108 results on '"Physiology"'
Search Results
2. CONTROL OF RENIN SECRETION.
- Author
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SKINNER SL, MCCUBBIN JW, and PAGE IH
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- Angiotensins, Biological Assay, Blood Circulation, Blood Flow Velocity, Carotid Arteries, Dogs, Hypoxia, Physiology, Renin, Research, Sensory Receptor Cells, Vagotomy
- Published
- 1964
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3. RENAL HYPERTENSION: AUTOREGULATION OF GLOMERULAR FILTRATION PRESSURE.
- Author
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STAHL WM
- Subjects
- Dogs, Angiotensins, Aortic Coarctation, Blood Pressure, Homeostasis, Hypertension, Hypertension, Renal, Juxtaglomerular Apparatus, Kidney, Kidney Glomerulus, Physiology, Pressure, Renin, Research
- Published
- 1964
- Full Text
- View/download PDF
4. THE JUXTAGLOMERULAR APPARATUS AND ALDOSTERONE IN HYPERALDOSTERONISM.
- Author
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TORIKAI T, FUKUCHI S, HANATA M, TAKAHASHI H, and DEMURA H
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- Humans, Aldosterone, Angiotensins, Biomedical Research, Carcinoma, Hepatocellular, Cushing Syndrome, Hepatitis, Hyperaldosteronism, Hypertension, Hypertension, Malignant, Hypertension, Renal, Juxtaglomerular Apparatus, Kidney, Liver Cirrhosis, Liver Neoplasms, Nephrotic Syndrome, Pathology, Peritonitis, Physiology, Renin, Stomach Neoplasms
- Published
- 1964
- Full Text
- View/download PDF
5. Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes
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Daniel M. Hinds, Heidi J. Nick, Tessa M. Vallin, Leslie A. Bloomquist, Sarah Christeson, Preston E. Bratcher, Emily H. Cooper, John T. Brinton, Angela Bosco-Lauth, and Carl W. White
- Subjects
Male ,Inflammation ,Vascular Endothelial Growth Factor A ,Pulmonary and Respiratory Medicine ,Nicotine ,Angiotensins ,Mesocricetus ,Superoxide Dismutase ,Tumor Necrosis Factor-alpha ,Physiology ,Vaping ,Cell Biology ,Electronic Nicotine Delivery Systems ,Fibrosis ,Thromboplastin ,Matrix Metalloproteinase 9 ,Transforming Growth Factor beta ,Cricetinae ,Physiology (medical) ,Renin ,Animals ,Matrix Metalloproteinase 2 ,Angiotensin-Converting Enzyme 2 ,Cotinine ,Transcriptome - Abstract
E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of subacute and chronic e-cigarette vaping exposure have shown many proinflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration of the animal or virus. Using a 2-day, whole body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung, and nasal histopathology, and gene expression in the nasopharynx and lung through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal–Wallis tests. For tests that were statistically significant ( P < 0.05), post hoc Tukey–Kramer and Dunn’s tests, respectively, were performed to make pairwise comparisons between groups. In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in gene expression associated with type 1 inflammation ( CCL-5 and CXCL-10), fibrosis [transforming growth factor-β ( TGF-β)], nicotine-independent increase oxidative stress response ( SOD-2), and a nicotine-independent decrease in vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway [angiotensin-converting enzyme ( ACE), ACE2], coagulation ( tissue factor, Serpine-1), extracellular matrix remodeling ( MMP-2, MMP-9), type 1 inflammation ( IL-1β, TNF-α, and CXCL-10), fibrosis ( TGF-β and Serpine-1), oxidative stress response ( SOD-2), neutrophil extracellular traps release ( ELANE), and vasculogenesis and angiogenesis ( VEGF-A) were identified. To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cigarette vaping. In addition, this is the first report that e-cigarette vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, neutrophil extracellular trap release (NETosis), vasculogenesis, and angiogenesis.
- Published
- 2022
6. Angiotensin-converting enzyme type 2 and aldosterone synthesis: beyond the renin--angiotensin--aldosterone system and closer to the clinic
- Author
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Ricardo A. Peña-Silva and Donald D. Heistad
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medicine.medical_specialty ,Angiotensins ,Aldosterone ,biology ,Physiology ,business.industry ,Angiotensin-converting enzyme ,Renin-Angiotensin System ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Renin ,Renin–angiotensin system ,Internal Medicine ,biology.protein ,medicine ,Humans ,Angiotensin-Converting Enzyme 2 ,Cardiology and Cardiovascular Medicine ,business - Published
- 2021
7. Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats.
- Author
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Chou, Chu-Lin, Lin, Heng, Chen, Jin-Shuen, and Fang, Te-Chao
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RENIN , *ANGIOTENSINS , *CARCINOGENESIS , *OBESITY , *ADIPOSE tissues - Abstract
Renin–angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar–Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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8. Natriuresis y hemodinámica glomerular en un incomprendido sistema renina angiotensina aldosterona.
- Author
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Castillo, Edwin Rolando
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KIDNEY glomerulus , *RENIN-angiotensin system , *ANGIOTENSINS , *CELL receptors , *CHRONIC kidney failure , *DIURESIS , *HEMODYNAMICS , *HYPERTENSION , *RENIN , *SODIUM , *PHYSIOLOGY - Abstract
Natriuretic response and glomerular hemodynamics depend on various intrarenal regulation systems; however, most of them possess some degree of dependence on the renin-angiotensin system. Tissue distribution and hemodynamic effects of this system are of vital importance for understanding of the natriuretic and glomerular filtration regulation in the context of different diseases characterized by dysregulation of sodium balance or glomerular filtration rate, such as nephrotic syndrome, acute and chronic renal failure and hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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9. Renin--angiotensin system blockers and the risk of critical or fatal coronavirus disease 2019 in African Americans
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Helena Michalopoulou and Costas Thomopoulos
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2019-20 coronavirus outbreak ,Angiotensins ,Coronavirus disease 2019 (COVID-19) ,Physiology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Angiotensin-Converting Enzyme Inhibitors ,medicine.disease_cause ,Renin-Angiotensin System ,Betacoronavirus ,Renin ,Renin–angiotensin system ,Internal Medicine ,Humans ,Medicine ,Pandemics ,Coronavirus ,SARS-CoV-2 ,business.industry ,COVID-19 ,medicine.disease ,Black or African American ,Pneumonia ,Immunology ,Coronavirus Infections ,business ,Cardiology and Cardiovascular Medicine - Published
- 2020
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10. Renin-Angiotensin System Hyperactivation Can Induce Inflammation and Retinal Neural Dysfunction.
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Kurihara, Toshihide, Ozawa, Yoko, Ishida, Susumu, Okano, Hideyuki, and Tsubota, Kazuo
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ALDOSTERONE antagonists , *RENIN-angiotensin system , *ANGIOTENSINS , *DIABETIC retinopathy , *GLAUCOMA , *INFLAMMATION , *PREVENTIVE health services , *RENIN , *RETINAL diseases , *RETINAL degeneration , *OXIDATIVE stress , *CHEMICAL inhibitors , *PHYSIOLOGY , *THERAPEUTICS - Abstract
The renin-angiotensin system (RAS) is a hormone system that has been classically known as a blood pressure regulator but is becoming well recognized as a proinflammatory mediator. In many diverse tissues, RAS pathway elements are also produced intrinsically, making it possible for tissues to respond more dynamically to systemic or local cues. While RAS is important for controlling normal inflammatory responses, hyperactivation of the pathway can cause neural dysfunction by inducing accelerated degradation of some neuronal proteins such as synaptophysin and by activating pathological glial responses. Chronic inflammation and oxidative stress are risk factors for high incidence vision-threatening diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. In fact, increasing evidence suggests that RAS inhibition may actually prevent progression of various ocular diseases including uveitis, DR, AMD, and glaucoma. Therefore, RAS inhibition may be a promising therapeutic approach to fine-tune inflammatory responses and to prevent or treat certain ocular and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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11. Liver X receptors alpha and beta regulate renin expression in vivo.
- Author
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Morello, Fulvio, de Boer, Rudolf A., Steffensen, Knut R., Gnecchi, Massimiliano, Chisholm, Jeffrey W., Boomsma, Frans, Anderson, Leonard M., Lawn, Richard M., Gustafsson, Jan-Åke, Lopez-Ilasaca, Marco, Pratt, Richard E., Dzau, Victor J., and Gustafsson, Jan-Ake
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RENIN , *LABORATORY mice , *LIVER , *HOMEOSTASIS , *PHYSIOLOGICAL control systems , *ANGIOTENSINS , *ANIMAL experimentation , *CELL lines , *CELL receptors , *CELLULAR signal transduction , *COMPARATIVE studies , *DNA , *GENES , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *NUCLEOTIDES , *RESEARCH , *DNA-binding proteins , *EVALUATION research , *RENIN-angiotensin system , *PHYSIOLOGY , *CELL physiology - Abstract
The renin-angiotensin-aldosterone system controls blood pressure and salt-volume homeostasis. Renin, which is the first enzymatic step of the cascade, is critically regulated at the transcriptional level. In the present study, we investigated the role of liver X receptor alpha (LXR(alpha)) and LXR(beta) in the regulation of renin. In vitro, both LXRs could bind to a noncanonical responsive element in the renin promoter and regulated renin transcription. While LXR(alpha) functioned as a cAMP-activated factor, LXR(beta) was inversely affected by cAMP. In vivo, LXRs colocalized in juxtaglomerular cells, in which LXR(alpha) was specifically enriched, and interacted with the renin promoter. In mouse models, renin-angiotensin activation was associated with increased binding of LXR(alpha) to the responsive element. Moreover, acute administration of LXR agonists was followed by upregulation of renin transcription. In LXR(alpha) mice, the elevation of renin triggered by adrenergic stimulation was abolished. Untreated LXR(beta) mice exhibited reduced kidney renin mRNA levels compared with controls. LXR(alpha)LXR(beta) mice showed a combined phenotype of lower basal renin and blunted adrenergic response. In conclusion, we show herein that LXR(alpha) and LXR(beta) regulate renin expression in vivo by directly interacting with the renin promoter and that the cAMP/LXR(alpha) signaling pathway is required for the adrenergic control of the renin-angiotensin system. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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12. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin.
- Author
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Ichihara, Atsuhiro, Hayashi, Matsuhiko, Kaneshiro, Yuki, Suzuki, Fumiaki, Nakagawa, Tsutomu, Tada, Yuko, Koura, Yukako, Nishiyama, Akira, Okada, Hirokazu, Uddin, M Nasir, Nabi, A H M Nurun, Ishida, Yuichi, Inagami, Tadashi, and Saruta, Takao
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DIABETES complications , *RENIN-angiotensin system , *ANGIOTENSINS , *ANIMAL experimentation , *BIOCHEMISTRY , *COMPARATIVE studies , *DIABETES , *DIABETIC nephropathies , *IMMUNOGLOBULINS , *KIDNEYS , *PHENOMENOLOGY , *RESEARCH methodology , *MEDICAL cooperation , *MOLECULAR structure , *PEPTIDES , *PROTEIN precursors , *PROTEINS , *RATS , *RENIN , *RESEARCH , *URINE , *ANGIOTENSIN II , *ANGIOTENSIN I , *EVALUATION research , *PREVENTION , *PHYSIOLOGY - Abstract
We found that when a site-specific binding protein interacts with the "handle" region of the prorenin prosegment, the prorenin molecule undergoes a conformational change to its enzymatically active state. This nonproteolytic activation is completely blocked by a decoy peptide with the handle region structure, which competitively binds to such a binding protein. Given increased plasma prorenin in diabetes, we examined the hypothesis that the nonproteolytic activation of prorenin plays a significant role in diabetic organ damage. Streptozotocin-induced diabetic rats were treated with subcutaneous administration of handle region peptide. Metabolic and renal histological changes and the renin-Ang system components in the plasma and kidneys were determined at 8, 16, and 24 weeks following streptozotocin treatment. Kidneys of diabetic rats contained increased Ang I and II without any changes in renin, Ang-converting enzyme, or angiotensinogen synthesis. Treatment with the handle region peptide decreased the renal content of Ang I and II, however, and completely inhibited the development of diabetic nephropathy without affecting hyperglycemia. We propose that the nonproteolytic activation of prorenin may be a significant mechanism of diabetic nephropathy. The mechanism and substances causing nonproteolytic activation of prorenin may serve as important therapeutic targets for the prevention of diabetic organ damage. [ABSTRACT FROM AUTHOR]
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- 2004
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13. CAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue.
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Serazin, Valérie, Dieudonné, Marie-Noelle, Morot, Mireille, de Mazandourt, Philippe, and Giudicelli, Yves
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PHYSIOLOGY , *METABOLISM , *ENDOCRINOLOGY , *RENIN-angiotensin system , *ALDOSTERONE , *ANGIOTENSINS , *RENIN - Abstract
The adipose renin-angiotensin system (RAS) has been assigned to participate in the control of adipose tissue development and in the pathogenesis of obesity-related hypertension. In adipose cells, the biological responses to β-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because cAMP is known to promote adipogenesis and because an association exists between body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in rat adipose tissue. Exposure of primary cultured differentiated preadipocytes to the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8BrcAMP) or cAMP-stimulating agents (forskolin and IBMX) results in a significant increase in ATG mRNA levels. In adipose tissue fragments, 8-BrcAMP also increases ATG mRNA levels and protein secretion, but not in the presence of the protein kinase A inhibitor H89. The addition of isoproterenol, known to stimulate the synthesis of intracellular cAMP via β-adrenoreceptors, had the same stimulatory effect on ATG expression and secretion. These results indicate that cAMP in vitro upregulates ATG expression and secretion in rat adipose tissue via the protein kinase A-dependent pathway. Further studies are required to determine whether this regulatory pathway is activated in human obesity, where increased sympathetic tone is frequently observed, and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state. [ABSTRACT FROM AUTHOR]
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- 2004
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14. Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production.
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Kobori, Hiroyuki, Harrison-Bernard, Lisa M, and Navar, L. Gabriel
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ANGIOTENSINS , *BLOOD pressure , *HOMEOSTASIS , *ANIMAL experimentation , *COMPARATIVE studies , *KIDNEYS , *RESEARCH methodology , *MEDICAL cooperation , *RATS , *RENAL hypertension , *RENIN , *RESEARCH , *SALT , *VASOCONSTRICTORS , *ANGIOTENSIN II , *EVALUATION research , *RENIN-angiotensin system , *PHARMACODYNAMICS , *PHYSIOLOGY - Abstract
Background: In rats maintained on a high salt diet (H/S) to suppress basal renal angiotensinogen levels, angiotensin II (Ang II) infusion for 13 days increased renal angiotensinogen mRNA and protein, thus providing a mechanism for further augmentation of intrarenal Ang II levels. The present study tested the hypothesis that enhanced intrarenal angiotensinogen formation during Ang II infusion is reflected by secretion into the tubular fluid leading to increased urinary excretion of angiotensinogen (UAGT).Methods: The effects of chronic Ang II infusion were examined on kidney and plasma Ang II levels and UAGT in male Sprague-Dawley rats maintained on an 8% salt diet for three weeks (N=10). Following one week on the H/S diet, Ang II (40 ng/min) was administered for two weeks via an osmotic minipump to one group (H/S + Ang II, N=5), while the remaining rats were sham-operated (H/S + Sham, N=5). Additionally, a control group was prepared with normal salt diet and sham-operation (N/S + Sham, N=5).Results: H/S alone did not alter systolic blood pressure (BP) (103 +/- 2 vs. 104 +/- 2 mm Hg), while Ang II infusion to H/S rats significantly increased systolic BP from 103 +/- 2 to 154 +/- 2 after two weeks. Intrarenal Ang II content in H/S + Ang II was significantly greater than H/S + Sham (435 +/- 153 vs. 65 +/- 14 fmol/g). Ang II infusion significantly increased UAGT (4.0 +/- 0.5 vs. 1.0 +/- 0.2 nmol Ang I/day by radioimmunoassay of generated Ang I; 57 +/- 15 vs. 14 +/- 2 densitometric units by Western blotting analysis) compared to Sham. UAGT by radioimmunoassay was highly correlated with kidney Ang II content (r=0.79); but not with plasma Ang II concentration (r=0.20).Conclusions: These data demonstrate that chronic Ang II infusion increases urinary excretion rate of angiotensinogen, and suggest that UAGT provides a specific index of intrarenal angiotensinogen production in Ang II-dependent hypertension. [ABSTRACT FROM AUTHOR]- Published
- 2002
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15. Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study.
- Author
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Rossing, Kasper, Christensen, Per K., Jensen, Berit R., and Parving, Hans-Henrik
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RENIN , *ANGIOTENSINS , *DIABETIC nephropathies , *PHYSIOLOGY - Abstract
Objective: Many patients with diabetic nephropathy (DN) have levels of albuminuria > 1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS).Research Design and Methods: We performed a randomized double-blind crossover study of 2 months treatment with candesartan cilexetil 8 mg once daily and placebo in addition to previous antihypertensive treatment. We included 18 type 2 diabetic patients with DN fulfilling the above-mentioned criteria. All received recommended doses of ACE inhibitor and, in addition, 15 patients received diuretics, 11 received a calcium channel antagonist, and 3 received a beta-blocker. At the end of each treatment period, we measured the glomerular filtration rate (GFR), 24-h blood pressure, albuminuria, and IgGuria.Results: The addition of candesartan to usual antihypertensive therapy induced a mean (95% CI) reduction in albuminuria of 25% (2-58), P = 0.036 (geometric mean [95% CI] from 1,764 mg/24 h [1,225-2,540] to 1,334 mg/24 h [890-1,998]). It also produced a mean reduction of 35% (9-53) in the fractional clearance of albumin (P = 0.016), a reduction of 32% (1-54) in fractional clearance of IgG (P = 0.046), a reduction in 24-h systolic blood pressure of 10 mmHg (2-18) (P = 0.019) (mean +/- +/- SE) from 148 +/- 3 to 138 +/- 5 mmHg, and a mean reduction in GFR of 5 ml. min(-1). 1.73 m(-2) (0.1-9) (P = 0.045).Conclusions: Dual blockade of the RAS reduces albuminuria and blood pressure in type 2 diabetic patients with DN responding insufficiently to previous antihypertensive therapy, including ACE inhibitors in recommended doses. [ABSTRACT FROM AUTHOR]- Published
- 2002
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16. Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system.
- Author
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Bergeron, Raynald, Kjaer, Michael, Simonsen, Lene, Bulow, Jens, Skovgaard, Dorthe, Howlett, Kirsten, and Galbo, Henrik
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RENIN , *ANGIOTENSINS , *BLOOD flow , *PHYSIOLOGY - Abstract
Presents a study which examined the implication of the renin-angiotensin system in regulation of splanchnic blood flow and glucose production in exercising humans. Methods; Results; Discussion.
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- 2001
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17. Role of the renin-angiotensin system during alterations of sodium intake in conscious mice.
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Cholewa, Brian C. and Mattson, David L.
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RENIN , *ANGIOTENSINS , *ALDOSTERONE , *SODIUM metabolism , *PHYSIOLOGY - Abstract
Presents a study which determined how the different components of the renin-angiotensin-aldosterone axis respond to alterations in sodium intake in conscious mice. Methods; Results; Discussion.
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- 2001
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18. Endothelin-A receptor antagonist inhibits angiotensin II and noradrenaline in man.
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Wenzel, R. R., Rüthemann, J., Bruck, H., Schäfers, R. F., Michel, M. C., and Philipp, Th.
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ENDOTHELINS , *SYMPATHETIC nervous system physiology , *RENIN , *ANGIOTENSINS , *PHYSIOLOGY - Abstract
Aims Endothelin-1 (ET-1) is a potent vasoconstrictor produced by the vascular endothelium. The interactions of ET with the mediators of the sympathetic nervous system and the renin-angiotensin-system in humans are unclear. Methods We studied the effects of the ETA-selective antagonist BQ-123 and the ETB-selective antagonist BQ-788 (both 10-10-10-8 m) on ET-1 (10-16-10-10 m), angiotensin II (AT, 10-16-10-10 m) and noradrenaline (NA, 10-16-10-10 m) induced vasoconstriction in the human skin microcirculation in vivo in 25 healthy male volunteers using laser Doppler flowmetry and double injection technique. Results BQ-123 caused a dose-dependent vasodilatation (maximum effect: + 949 ± 84 AUC-PU, P < 0.001), whereas BQ-788 induced mild vasoconstriction (maximum effect: -388 ± 96 AUC-PU, P < 0.01). In the presence of BQ-123, but not BQ-788, ET-1, AT and NA caused markedly less vasoconstriction at any tested agonist dose; the effect was most pronounced on ET-1 (maximum effect at 10-14 m: + 814 ± 93 AUC-PU vs ET alone, P < 0.001), followed by noradrenaline (maximim effect at 10-16 m: + 580 ± 107 AUC-PU vs NA alone, P < 0.01) and angiotensin II (maximim effect at 10-14 m: + 493 ± 111 AUC-PU vs AT alone, P < 0.001). Conclusions ETA-selective antagonism inhibits vasoconstriction to AT and NA in vivo in healthy subjects. This beneficial effect may be useful for the treatment of patients with cardiovascular disease including hypertension especially in combination therapy with sympatholytic agents and inhibitors of the renin-angiotensin system. [ABSTRACT FROM AUTHOR]
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- 2001
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19. Effects of converting enzyme inhibitors on renal P-450 metabolism of arachidonic acid.
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Ito, Osamu and Omata, Ken
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RENIN , *KIDNEYS , *ANGIOTENSINS , *ARACHIDONIC acid , *RAT physiology , *BIOCHEMICAL mechanism of action , *METABOLISM , *PHYSIOLOGY - Abstract
Presents information on a study which examined the effects of blockade of the renin-angiotensin system on the renal metabolism of arachidonic acid in rats. Methods used; Results; Discussion.
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- 2001
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20. Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure.
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Hiroya Kawai and Stevens, Suzanne Y.
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RENIN , *ANGIOTENSINS , *INNERVATION of the heart , *HEART failure , *PATHOLOGICAL physiology , *PHYSIOLOGY - Abstract
Presents a study which determined the effect of renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure. Methods; Results; Discussion.
- Published
- 2000
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21. Renin-angiotension system and sympathetic nervous system in cardiac pressure-overload hypertrophy.
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Akers, Wendell S. and Cross, Andrew
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CARDIAC hypertrophy , *ANGIOTENSINS , *RENIN , *SYMPATHETIC nervous system , *PHYSIOLOGY - Abstract
Presents a study which determined the temporal sequence for activation of the renin-angiotensin and sympathetic nervous system in response to cardiac pressure overload. Factors which offset the benefits of cardiac hypertrophy; Methodology; Results and discussion.
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- 2000
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22. Role of renin-angiotensin system in drinking of seawater-adapted eels Anguilla japonica: a reevaluation.
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Takei, Yoshio and Tsuchida, Takamasa
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RENIN , *DRINKING (Physiology) , *ANGIOTENSINS , *EELS , *PHYSIOLOGY - Abstract
Presents information on a study which evaluated the role of endogenous renin-angiotensin system in copius drinking of seawater eels. Methodology; Effects of SQ-14225 and an anti-ANG II serum on drinking, plasma ANG II hormone, and blood pressure; Role of ANG II hormone in drinking of seawater fish.
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- 2000
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23. Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system.
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Greenleaf, John E. and Petersen, Trine Wellow
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RENIN , *PHYSIOLOGY of men , *CEREBRAL circulation , *ANGIOTENSINS , *CHEMICAL inhibitors , *PHYSIOLOGY - Abstract
Focuses on a study which discussed the low lower body negative pressure tolerance in men associated with attenuation of the renin-angiotensin system. Information on the mechanisms for reduction of cerebral blood pressure; Methodology; Results of the study.
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- 2000
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24. Evidence for an intrarenal renin-angiotensin system in the rainbow trout, Oncorhynchus mykiss.
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Brown, J. Anne and Paley, Richard K.
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RAINBOW trout , *RENIN , *ANGIOTENSINS , *PHYSIOLOGY - Abstract
Presents information on a study which investigated the existence of an intrarenal renin-angiotensin system in rainbow trout. Materials and methods; Results and discussion.
- Published
- 2000
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25. The Renin-Angiotensin System: Physiology, Pathophysiology, and Pharmacology.
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Reid, Ian A.
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RENIN , *ANGIOTENSINS , *PHYSIOLOGY - Abstract
Discusses how the author teaches the subject of the renin-angiotensin system in the areas of physiology, pathophysiology and pharmacology. Significance of the system; Discussion on the biosynthesis of angiotensin II; Role of angiotensin in body fluid and blood pressure regulation.
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- 1998
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26. Renal growth and development in mice lacking AT1A...
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Oliverio, Michael I., Madsen, Kirsten, Best, Christopher F., Ito, Masaki, Maeda, Nobuyo, Smithies, Oliver, and Coffman, Thomas M.
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RENIN , *ANGIOTENSINS , *BLOOD pressure , *BIOCHEMICAL mechanism of action , *PHYSIOLOGY - Abstract
Examines the role of the type 1A (AT1A) angiotensin receptor in renal growth and development. Involvement of renin-angiotensin system (RAS) in the regulation of blood pressure; Determining the role of AT1A receptor in mediating functions related to organogenesis and development; Experimental procedure used in the study; Discussion of the results obtained from the study.
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- 1998
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27. Distinct localization of renin and GLUT-4 in...
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Anderson, Timothy J., Martin, Sally, Berka, Jennifer L., James, David E., Slot, Jan W., and Stow, Jennifer L.
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RENIN , *ANGIOTENSINS , *JUXTAGLOMERULAR apparatus physiology , *PHYSIOLOGY , *BIOSYNTHESIS - Abstract
Examines the distinct location of renin and insulin responsive glucose transporter (GLUT-4) in the juxtaglomerular cells of mouse kidney. Location of GLUT-4 in the mouse cells; Physiologic functions of renin in the formation of angiotensin II; Materials and methods used in the study; Discussion of the results obtained in the experiment.
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- 1998
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28. Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy
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Kirsty G. Pringle and Eugenie R. Lumbers
- Subjects
Kidney ,medicine.medical_specialty ,Pregnancy ,Angiotensins ,Physiology ,Decidua ,Biology ,medicine.disease ,Renin-Angiotensin System ,medicine.anatomical_structure ,Endocrinology ,Physiology (medical) ,Placenta ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Humans ,Female ,Receptor ,Aldosterone ,Homeostasis ,Hormone - Abstract
This review describes the changes that occur in circulating renin-angiotensin-aldosterone system (RAAS) components in human pregnancy. These changes depend on endocrine secretions from the ovary and possibly the placenta and decidua. Not only do these hormonal secretions directly contribute to the increase in RAAS levels, they also cause physiological changes within the cardiovascular system and the kidney, which, in turn, induce reflex release of renal renin. High levels of ANG II play a critical role in maintaining circulating blood volume, blood pressure, and uteroplacental blood flow through interactions with the ANG II type I receptor and through increased production of downstream peptides acting on a changing ANG receptor phenotype. The increase in ANG II early in gestation is driven by estrogen-induced increments in angiotensinogen (AGT) levels, so there cannot be negative feedback leading to reduced ANG II production. AGT can exist in various forms in terms of redox state or complexed with other proteins as polymers; these affect the ability of renin to cleave ANG I from AGT. Thus, during pregnancy the rate of ANG I production varies not only because levels of renin change in response to homeostatic demand but also because AGT changes not only in concentration but in form. Activation of the circulating and intrarenal RAASs is essential for normal pregnancy outcome subserving the increased demand for salt and, hence, water during pregnancy. Thus, the complex integration of the secretions and actions of the circulating maternal renin-angiotensin system in pregnancy plays a key role in pregnancy outcome.
- Published
- 2014
29. Subcellular characteristics of functional intracellular renin–angiotensin systems
- Author
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Jeremy D. Walston, Peter M. Abadir, and Robert M. Carey
- Subjects
medicine.medical_specialty ,Angiotensin receptor ,Angiotensins ,Physiology ,Cell ,Biochemistry ,Article ,Renin-Angiotensin System ,Cellular and Molecular Neuroscience ,Paracrine signalling ,Endocrinology ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Extracellular ,Animals ,Humans ,biology ,Angiotensin-converting enzyme ,Subcellular localization ,Cell biology ,medicine.anatomical_structure ,biology.protein ,Intracellular - Abstract
The renin–angio tensin system (RAS) is now regarded as an integral component in not only the development of hypertension, but also in physiologic and pathophysiologic mechanisms in multiple tissues and chronic disease states. While many of the endocrine (circulating), paracrine (cell-to-different cell) and autacrine (cell-to-same cell) effects of the RAS are believed to be mediated through the canonical extracellular RAS, a complete, independent and differentially regulated intracellular RAS (iRAS) has also been proposed. Angiotensinogen, the enzymes renin and angiotensin-converting enzyme (ACE) and the angiotensin peptides can all be synthesized and retained intracellularly. Angiotensin receptors (types I and 2) are also abundant intracellularly mainly at the nuclear and mitochondrial levels. The aim of this review is to focus on the most recent information concerning the subcellular localization, distribution and functions of the iRAS and to discuss the potential consequences of activation of the subcellular RAS on different organ systems.
- Published
- 2012
30. Divergent pathways for the angiotensin-(1–12) metabolism in the rat circulation and kidney
- Author
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Mark C. Chappell and Brian M. Westwood
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Physiology ,Angiotensinogen ,Angiotensin-Converting Enzyme Inhibitors ,Endogeny ,Peptidyl-Dipeptidase A ,Kidney ,Biochemistry ,Article ,Cellular and Molecular Neuroscience ,Endocrinology ,Lisinopril ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,Neprilysin ,Chemistry ,Angiotensin II ,Metabolism ,Peptide Fragments ,Rats ,medicine.anatomical_structure ,Rats, Inbred Lew ,Hypertension ,ACE inhibitor ,cardiovascular system ,Angiotensin I ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Evidence of endogenous angiotensin-(1–12) [Ang-(1–12)] may necessitate revision of the accepted view that Ang I is the immediate peptide product derived from the precursor protein angiotensinogen. As the processing of this peptide has not been fully elucidated, we characterized Ang-(1–12) metabolism in the serum and kidney of the mRen2.Lewis rat, a model of high circulating renin and ACE expression. A sensitive HPLC-based method to detect the metabolism ex vivo of low concentrations of 125 I-labeled Ang-(1–12) was utilized. Ang-(1–12) processing to serum did not reveal the participation of renin; however, serum ACE readily converted Ang-(1–12) to Ang I with subsequent metabolism to Ang II. Ang I and Ang II forming activities for serum ACE were 102 ± 4 and 104 ± 3 fmol/ml/min serum ( n = 3), respectively, and both products were abolished by the potent ACE inhibitor lisinopril. The metabolism of Ang-(1–12) in renal cortical membranes also revealed the formation of Ang I; however, the main products were Ang-(1–7) and Ang-(1–4) at 129 ± 9 and 310 ± 12 fmol/mg/min protein ( n = 4), respectively. Neprilysin inhibition abolished these products and substantially reduced the overall metabolism of Ang-(1–12). Incubation of Ang-(1–12) with either human or mouse neprilysin revealed identical products. We conclude that endogenous Ang-(1–12) may contribute to the expression of biologically active angiotensins through a renin-independent pathway. The preferred route for Ang-(1–12) metabolism likely reflects the relative tissue content of ACE and neprilysin.
- Published
- 2012
31. Physiology of Kidney Renin
- Author
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Frank Schweda, Hayo Castrop, Charlotte Wagner, Klaus Höcherl, Vladimir T. Todorov, and Armin Kurtz
- Subjects
Kidney ,Angiotensins ,Protease ,Physiology ,medicine.medical_treatment ,General Medicine ,Biology ,Bioinformatics ,medicine.anatomical_structure ,Gene Expression Regulation ,Physiology (medical) ,Renin ,Renin–angiotensin system ,Immunology ,medicine ,Animals ,Humans ,Molecular Biology ,Signal Transduction - Abstract
The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).
- Published
- 2010
32. Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2)27 hypertensive rats
- Author
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Debra I. Diz, Ellen N. Tommasi, Katsunori Isa, Carlos M. Ferrario, Detlev Ganten, Maria A. Garcia-Espinosa, Amy C. Arnold, Nancy T. Pirro, and Mark C. Chappell
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Time Factors ,Physiology ,Transgene ,Central nervous system ,Angiotensinogen ,Drinking ,Hemodynamics ,Blood Pressure ,Immunoglobulin G ,Eating ,Physiology (medical) ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,biology ,Angiotensin 1 ,business.industry ,Body Weight ,Osmolar Concentration ,Brain ,Articles ,Infusion Pumps, Implantable ,Peptide Fragments ,Rats ,Disease Models, Animal ,Urodynamics ,medicine.anatomical_structure ,Endocrinology ,Blood pressure ,Hypertension ,biology.protein ,Rats, Transgenic ,Antibody ,business - Abstract
Angiotensin-(1-12) [ANG-(1-12)] is a newly identified peptide detected in a variety of rat tissues, including the brain. To determine whether brain ANG-(1-12) participates in blood pressure regulation, we treated male adult (mRen2)27 hypertensive rats (24–28 wk of age) with Anti-ANG-(1-12) IgG or Preimmune IgG via an intracerebroventricular cannula for 14 days. Immunoneutralization of brain ANG-(1-12) lowered systolic blood pressure (−43 ± 8 mmHg on day 3 and −26 ± 7 mmHg on day 10 from baseline, P < 0.05). Water intake was lower on intracereroventricular day 6 in the Anti-ANG-(1-12) IgG group, accompanied by higher plasma osmolality on day 13, but there were no differences in urine volume, food intake, or body weight during the 2-wk treatment. In Preimmune IgG-treated animals, there were no significant changes in these variables over the 2-wk period. The antihypertensive effects produced by endogenous neutralization of brain ANG-(1-12) suggest that ANG-(1-12) is functionally active in brain pathways regulating blood pressure.
- Published
- 2009
33. Enzymatic pathways of the brain renin–angiotensin system: Unsolved problems and continuing challenges
- Author
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Vardan T. Karamyan and Robert C. Speth
- Subjects
Angiotensin receptor ,Angiotensins ,Physiology ,Clinical Biochemistry ,Central nervous system ,Biology ,Biochemistry ,Models, Biological ,Article ,Radioligand binding assays ,Cellular and Molecular Neuroscience ,Endocrinology ,Renin–angiotensin system ,Endopeptidases ,Renin ,Radioligand ,medicine ,Animals ,Humans ,Receptor ,Receptors, Angiotensin ,Brain ,Angiotensin receptors ,Angiotensin II ,Angiotensin receptor binding ,medicine.anatomical_structure ,Metabolism ,Signal transduction ,Angiotensinases ,Peptidases ,Neuroscience ,Peptide Hydrolases ,Signal Transduction - Abstract
The brain renin-angiotensin system continues to be enigmatic more than 40 years after the brain was first recognized to be a site of action of angiotensin II. This review focuses on the enzymatic pathways for the formation and degradation of the growing number of active angiotensins in the brain. A brief description and nomenclature of the peptidases involved in the processing of angiotensin peptides in the brain is given. Of primary interest is the array of enzymes that degrade radiolabeled angiotensins in receptor binding assays. This poses major challenges to studies of brain angiotensin receptors and it is debatable whether an accurate determination of brain angiotensin receptor binding kinetics has yet been made. The quandary facing the investigator of brain angiotensin receptors is the need to protect the radioligand from metabolic alteration while maintaining the characteristics of the receptors in situ. It is the tenet of this review that we have yet to fully understand the binding characteristics of brain angiotensin receptors and the extent of their distribution in the brain because of our inability to fully protect the angiotensins from metabolic alteration until equilibrium binding conditions can be attained.
- Published
- 2007
34. Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options
- Author
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Ashley L. Wagoner, Debra I. Diz, John E. Fortunato, and Hossam A. Shaltout
- Subjects
Male ,Supine position ,Angiotensins ,Adolescent ,Epinephrine ,Cardiovascular Neurohormonal Regulation ,Physiology ,Systole ,Vasopressins ,Dopamine ,Orthostatic intolerance ,Blood Pressure ,030204 cardiovascular system & hematology ,Syncope ,03 medical and health sciences ,Tilt table test ,Orthostatic vital signs ,Hypotension, Orthostatic ,Norepinephrine ,Postural Orthostatic Tachycardia Syndrome ,0302 clinical medicine ,Catecholamines ,Diastole ,Heart Rate ,Tilt-Table Test ,Physiology (medical) ,Heart rate ,Renin ,medicine ,Humans ,Arterial Pressure ,Prospective Studies ,Child ,Aldosterone ,medicine.diagnostic_test ,business.industry ,Angiotensin II ,medicine.disease ,Blood pressure ,Anesthesia ,Orthostatic Intolerance ,Female ,Angiotensin I ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10–18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.
- Published
- 2015
35. Differential modulation of baroreflex control of heart rate by neuron- vs. glia-derived angiotensin II
- Author
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Koji Sakai, Mark W. Chapleau, Martin D. Cassell, Satoshi Morimoto, and Curt D. Sigmund
- Subjects
Nitroprusside ,Genetically modified mouse ,medicine.medical_specialty ,Sympathetic nervous system ,Angiotensins ,Physiology ,Angiotensinogen ,Blood Pressure ,Mice, Transgenic ,Biology ,Baroreflex ,Cardiovascular Physiological Phenomena ,Mice ,Phenylephrine ,Heart Rate ,Internal medicine ,Renin ,Heart rate ,Renin–angiotensin system ,Genetics ,medicine ,Animals ,Humans ,Neurons ,Differential modulation ,Angiotensin II ,Brain ,Immunohistochemistry ,Propranolol ,Endocrinology ,medicine.anatomical_structure ,cardiovascular system ,Neuron ,Peptides ,Neuroglia ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology - Abstract
We developed transgenic mice with targeted expression of human renin (hREN) and human angiotensinogen (hAGT) to either neurons (N-AII mice) or glia (G-AII mice) to test the hypothesis that neuronal and glial ANG II may have differential function. Since baseline blood pressure (BP) did not differ between the models (109 ± 3 vs. 114 ± 4 mmHg), we stressed the BP regulatory pathway by measuring the heart rate (HR) (baroreflex) response to phenylephrine- and nitroprusside-induced changes in arterial BP. The midpoint of the baroreflex curve (BP50) was reset to a significantly higher BP in N-AII mice (131 ± 5 mmHg) compared with littermate controls (115 ± 3 mmHg). Baroreflex gain (slope of BP-HR relation) was similar in N-AII and control mice (12 ± 1 vs. 14 ± 2 beats·min−1·mmHg−1). In contrast, G-AII mice exhibited less of an increase in BP50 (125 ± 5 mmHg) but a larger decrease in baroreflex gain (8 ± 1 beats·min−1·mmHg−1) compared with both control and N-AII mice. Differences in BP50 and gain between N-AII, G-AII, and control mice persisted after parasympathetic blockade with atropine but were eliminated after sympathetic blockade with propranolol, indicating the effects of ANG II were selective for cardiosympathetic arm of the reflex. ANG II-like immunoreactivity was observed more prominently around the paraventricular nucleus and nucleus tractus solitarii in G-AII mice but more prominently in the ventrolateral medulla in N-AII mice. We conclude that ANG II differentially modulates baroreflex control of HR in mice producing ANG II in neurons vs. glia, and its differential function may reflect regional differences in the production of ANG II in cardiovascular control nuclei of the brain.
- Published
- 2004
36. Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults
- Author
-
Linda R. Peterson, Robert J. Spina, Christopher J Koenig, Ali A. Ehsani, Christa R Florence, and Morton R. Rinder
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Angiotensins ,Physiology ,Sodium Chloride Symporter Inhibitors ,Hemodynamics ,Blood Pressure ,Physical exercise ,Ventricular Dysfunction, Left ,Oxygen Consumption ,Insulin resistance ,Hydrochlorothiazide ,Heart Rate ,Physiology (medical) ,Internal medicine ,Renin ,Heart rate ,medicine ,Hyperinsulinemia ,Humans ,Plasma Volume ,Exercise physiology ,Diuretics ,Exercise ,Aged ,business.industry ,Blood Pressure Monitoring, Ambulatory ,medicine.disease ,Lipids ,Blood pressure ,Endocrinology ,Hypertension ,Body Composition ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Insulin Resistance ,business ,medicine.drug - Abstract
To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 ± 1.3 yr; n = 16) that exercised or to a group (age 65.3 ± 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 ± 12.2 vs. 11.5 ± 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio ( h/ r) similarly (exercise: before 0.48 ± 0.2, after 0.42 ± 0.01; thiazide: before 0.47 ± 0.04, after 0.40 ± 0.04; P = 0.017). The reductions in systolic BP and h/ r were correlated in the exercise group ( r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 ± 2.6 vs. 9.84 ± 1.5 mU·ml−1·min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people.
- Published
- 2004
37. Renin, Angiotensin, Sodium and Organ Damage
- Author
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Trefor Morgan
- Subjects
medicine.medical_specialty ,Angiotensin receptor ,Angiotensins ,Physiology ,Internal medicine ,Renin ,Renin–angiotensin system ,Internal Medicine ,medicine ,Animals ,Humans ,Angiotensin II receptor type 1 ,biology ,business.industry ,Sodium ,Angiotensin-converting enzyme ,Angiotensin II ,Endocrinology ,Losartan ,Blood pressure ,Hypertension ,ACE inhibitor ,biology.protein ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Angiotensin II and sodium balance affect the status of each other and both--either separately or together--can lead to an increase in blood pressure. They also can cause vascular and cardiac damage due to direct effects and effects mediated by the blood pressure increase. This paper reviews the important interactions among these three variables. Acute blood pressure elevation during sleeping but not during waking hours causes cardiac hypertrophy in rats. Similarly, lowering of blood pressure with an angiotension converting enzyme (ACE) inhibitor during sleep but not when awake causes regression of cardiac hypertrophy in rats with 2kidney (K)-1clip (C) Goldblatt hypertension. If angiotensin is given to rats on a low (0.4%) NaCl diet, blood pressure rises but there is less cardiac hypertrophy. Cardiac hypertrophy is greatest after angiotensin administration in rats on a high (4%) NaCl diet. In both the 2K-1C and 1K-1C Goldblatt models, a high salt intake reduces the blood pressure lowering effect of captopril and losartan and prevents regression of cardiac hypertrophy. Combined administration of an ACE inhibitor and an angiotensin type 1 (AT1) receptor blocker to rats on a low (0.2%) NaCl diet produces a syndrome that leads to death with cardiac involution. All features of the syndrome are reversed or prevented by 4% NaCl intake. It is hypothesised that the interaction between angiotensin II and sodium intake can be explained by differences in the way protons produced by contracting cells are neutralized. The sodium hydrogen exchanger and the sodium 2 bicarbonate cotransporter are stimulated by the AT1 and angiotensin type 2 (AT2) receptor, respectively. If the ratio of receptors is altered in favour of the AT2 receptor, then less cardiac hypertrophy will result from the same workload. Review of the clinical literature reveals that many of these results in rats have correlations in clinical medicine. Thus high night time blood pressure is associated with a greater morbidity and high salt intake causes cardiac hypertrophy and vascular stiffness independent of blood pressure levels. When deciding on treatment in human hypertension these results have important clinical implications.
- Published
- 2003
38. Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood
- Author
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Jean St-Louis, Michèle Brochu, Marie-Claude Battista, and Luc L. Oligny
- Subjects
Male ,Aging ,medicine.medical_specialty ,Angiotensins ,Physiology ,Heart Ventricles ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Kidney Glomerulus ,Intrauterine growth restriction ,Renal function ,Blood Pressure ,Kidney ,Kidney Function Tests ,Rats, Sprague-Dawley ,Renin-Angiotensin System ,chemistry.chemical_compound ,Pregnancy ,Physiology (medical) ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,RNA, Messenger ,reproductive and urinary physiology ,Creatinine ,Fetal Growth Retardation ,business.industry ,Body Weight ,Organ Size ,medicine.disease ,female genital diseases and pregnancy complications ,Rats ,medicine.anatomical_structure ,Blood pressure ,Endocrinology ,chemistry ,Hypertension ,embryonic structures ,Gestation ,Female ,Kidney Diseases ,Corticosterone ,business ,Atrial Natriuretic Factor - Abstract
Epidemiological studies have produced evidence that unfavorable intrauterine environments during fetal life may lead to adverse outcomes in adulthood. We have previously shown that a low-sodium diet, given to pregnant rats over the last week of gestation, results in intrauterine growth restriction (IUGR). We hypothesize that pups born with IUGR are more susceptible to the development of hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for organ growth and renal morphogenesis. The adults (12 wk) were evaluated for weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone system (RAAS), and renal function; hearts and kidneys underwent a histological examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR fetuses compared with age-matched controls, whereas the kidney-to-body ratio was unchanged. Systolic blood pressure was elevated in both IUGR male and female adults. Plasma aldosterone levels were not correlated with increased plasma renin activity. Moreover, urinary sodium was decreased, whereas plasma urea was elevated in both males and females, and creatinine levels were augmented only in females, suggesting a glomerular filtration impairment in IUGR. In our model of IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure, alteration of the RAAS, and renal dysfunction are observed in adult life. Differences observed between male and female adults suggest the importance of gender in outcomes in adulthood after IUGR.
- Published
- 2002
39. Functional Significance of Prorenin Internalization in the Rat Heart
- Author
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Matthew G.F. Sharp, Susanne Clausmeyer, John J. Mullins, Jörg Peters, Jutta Zimmer, Raphaela Farrenkopf, and Surasak Kantachuvesiri
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Glycosylation ,Physiology ,media_common.quotation_subject ,Transgene ,Biology ,Animals, Genetically Modified ,Rats, Sprague-Dawley ,Pathogenesis ,chemistry.chemical_compound ,Fibrosis ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,RNA, Messenger ,Internalization ,Receptor ,Cells, Cultured ,media_common ,Enzyme Precursors ,Myocardium ,fungi ,medicine.disease ,Endocytosis ,Rats, Inbred F344 ,Rats ,Endocrinology ,chemistry ,Cardiology and Cardiovascular Medicine ,Intracellular - Abstract
Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2 d renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.
- Published
- 2002
40. Insulin‐like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep
- Author
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Julie A. Owens, Amanda C. Marsh, Karen J. Gibson, Eugenie R. Lumbers, June Wu, and Phillip C. Owens
- Subjects
medicine.medical_specialty ,Angiotensins ,Physiology ,Renal function ,Blood Pressure ,Gestational Age ,Kidney ,Plasma renin activity ,Renin-Angiotensin System ,Fetal Heart ,Fetus ,Heart Rate ,Internal medicine ,Renin ,medicine ,Animals ,Insulin-Like Growth Factor I ,Acid-Base Equilibrium ,Sheep ,Chemistry ,Reabsorption ,Original Articles ,Hydrogen-Ion Concentration ,Fetal Blood ,Filtration fraction ,Free water clearance ,Endocrinology ,medicine.anatomical_structure ,Renal physiology ,Renal blood flow ,Gases - Abstract
While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin-angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 ug h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). Plasma renin concentration increased by 275 +/- 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth.
- Published
- 2001
41. When pouring water on the fire makes it burn brighter
- Author
-
Alan M. Fogelman
- Subjects
Angiotensins ,Arteriosclerosis ,Physiology ,Blood Pressure ,Biology ,Ion Channels ,Muscle, Smooth, Vascular ,Mitochondrial Proteins ,Mice ,Smooth muscle ,Renin ,Animals ,Humans ,Molecular Biology ,Phospholipids ,Uncoupling Protein 1 ,Inflammation ,chemistry.chemical_classification ,Reactive oxygen species ,Membrane Proteins ,Cell Biology ,Thermogenin ,Cell biology ,Blood pressure ,Biochemistry ,chemistry ,Carrier Proteins ,Reactive Oxygen Species - Abstract
Earlier work seems to suggest that overexpression of uncoupling protein 1 would be anti-inflammatory. However, new findings show that expression of uncoupling protein 1 in aortic smooth muscle cells of mice increases reactive oxygen species, activates the renin-angiotensin system, elevates blood pressure, and worsens atherosclerosis.
- Published
- 2005
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42. Increased dietary NaCl potentiates the effects of elevated prorenin levels on blood pressure and organ disease
- Author
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Duncan J. Campbell, Patrick Bruneval, Joël Ménard, John J. Mullins, and Habib Karam
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Cardiac fibrosis ,Physiology ,Blood Pressure ,Cardiomegaly ,Peptide hormone ,Article ,Muscle hypertrophy ,Random Allocation ,Fibrosis ,Internal medicine ,Renin ,Renin–angiotensin system ,Internal Medicine ,Animals ,Medicine ,Sodium Chloride, Dietary ,Retrospective Studies ,Enzyme Precursors ,business.industry ,Angiotensin II ,fungi ,medicine.disease ,Rats ,Endocrinology ,Blood pressure ,Hypertension ,Kidney Diseases ,Myocardial fibrosis ,Rats, Transgenic ,business ,Cardiology and Cardiovascular Medicine ,Chymosin - Abstract
Background Rats with several 100-fold elevation of plasma prorenin levels due to liver-specific expression of a rat prorenin transgene have cardiac and aortic hypertrophy, renal lesions, and myocardial fibrosis. The effect of increased dietary NaCl on the phenotype of prorenin transgenic rats has not been examined.Methods and results We compared the effects of 0.3 and 2% dietary NaCl in wild-type and transgenic rats from 3 to 12 months of age. In comparison with wild-type rats, transgenic rats receiving 0.3% dietary NaCl had approximately 1000-fold elevation of prorenin, 1.5-fold to 2.5-fold elevation of renin concentration and activity, wildtype levels of angiotensin II, and were hypertensive with cardiac and aortic hypertrophy, and increased renal glomerular and tubulo-interstitial injury score. In wild-type rats, 2% dietary NaCl reduced angiotensin levels, produced a delayed increase in blood pressure, and caused cardiac hypertrophy and tubulo-interstitial injury. By contrast, 2% NaCl did not reduce angiotensin levels in transgenic rats, potentiated their hypertension, cardiac and aortic hypertrophy, and increased myocardial interstitial and perivascular fibrosis, without effect on glomerular or tubulointerstitial injury score.Conclusion Increased dietary NaCl had a greater impact on the phenotype of transgenic than wild-type rats that may have been due, in part, to their hypertension and their failure to suppress angiotensin levels, consequent to their elevated prorenin levels. J Hypertens 28: 1429-1437 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
- Published
- 2010
43. Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy
- Author
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Sayaka Nagata, Carlos M. Ferrario, James R. Sowers, Aaron J. Trask, Jasmina Varagic, Johji Kato, Kazuo Kitamura, Mark C. Chappell, Adam Whaley-Connell, and Javad Habibi
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Physiology ,medicine.medical_treatment ,Angiotensinogen ,Hemodynamics ,Peptide hormone ,Kidney ,Nephrectomy ,Rats, Inbred WKY ,Renin-Angiotensin System ,Physiology (medical) ,Internal medicine ,Renin–angiotensin system ,Renin ,medicine ,Animals ,RNA, Messenger ,business.industry ,Angiotensin II ,Myocardium ,Articles ,Peptide Fragments ,Rats ,medicine.anatomical_structure ,Endocrinology ,Circulatory system ,Models, Animal ,cardiovascular system ,Angiotensin I ,Cardiology and Cardiovascular Medicine ,business ,hormones, hormone substitutes, and hormone antagonists ,Bilateral Nephrectomy - Abstract
We examined the effects of 48 h bilateral nephrectomy on plasma and cardiac tissue expression of angiotensin-(1-12) [ANG-(1-12)], ANG I, and ANG II in adult Wistar-Kyoto rats to evaluate functional changes induced by removing renal renin. The goal was to expand the evidence of ANG-(1-12) being an alternate renin-independent, angiotensin-forming substrate. Nephrectomy yielded divergent effects on circulating and cardiac angiotensins. Significant decreases in plasma ANG-(1-12), ANG I, and ANG II levels postnephrectomy accompanied increases in cardiac ANG-(1-12), ANG I, and ANG II concentrations compared with controls. Plasma ANG-(1-12) decreased 34% following nephrectomy, which accompanied 78 and 66% decreases in plasma ANG I and ANG II, respectively ( P < 0.05 vs. controls). Contrastingly, cardiac ANG-(1-12) in anephric rats averaged 276 ± 24 fmol/mg compared with 144 ± 20 fmol/mg in controls ( P < 0.005). Cardiac ANG I and ANG II values were 300 ± 15 and 62 ± 7 fmol/mg, respectively, in anephric rats compared with 172 ± 8 fmol/mg for ANG I and 42 ± 4 fmol/mg for ANG II in controls ( P < 0.001). Quantitative immunofluorescence revealed significant increases in average grayscale density for cardiac tissue angiotensinogen, ANG I, ANG II, and AT1 receptors of WKY rats postnephrectomy. Faint staining of cardiac renin, unchanged by nephrectomy, was associated with an 80% decrease in cardiac renin mRNA. These changes were accompanied by significant increases in p47phox, Rac1, and Nox4 isoform expression. In conclusion, ANG-(1-12) may be a functional precursor for angiotensin peptide formation in the absence of circulating renin.
- Published
- 2009
44. Angiotensin-(1–12) is an alternate substrate for angiotensin peptide production in the heart
- Author
-
Jewell A. Jessup, Aaron J. Trask, Carlos M. Ferrario, and Mark C. Chappell
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Time Factors ,Physiology ,Prohormone ,Angiotensinogen ,Peptide ,Peptide hormone ,Rats, Inbred WKY ,Article ,Animals, Genetically Modified ,Rats, Sprague-Dawley ,Renin-Angiotensin System ,Physiology (medical) ,Internal medicine ,Rats, Inbred SHR ,Renin–angiotensin system ,Renin ,medicine ,Animals ,chemistry.chemical_classification ,biology ,Chemistry ,Angiotensin II ,Myocardium ,Angiotensin-converting enzyme ,Peptide Fragments ,Rats ,Perfusion ,Disease Models, Animal ,Endocrinology ,Rats, Inbred Lew ,Circulatory system ,Hypertension ,biology.protein ,Angiotensin I ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Identification of angiotensin-(1-12) as an intermediate precursor derived directly from angiotensinogen led us to explore whether the heart has the capacity to process angiotensin-(1-12) into biologically active angiotensin peptides. The generation of angiotensin I, angiotensin II, and angiotensin-(1-7) from exogenous angiotensin-(1-12) was evaluated in the effluent of isolated perfused hearts mounted on a Langendorff apparatus in three normotensive and two hypertensive strains: Sprague-Dawley, Lewis, congenic mRen2.Lewis, Wistar-Kyoto, and spontaneously hypertensive rats. Hearts were perfused with Krebs solution for 60 min before and after the addition of angiotensin-(1-12) (10 nmol/l). Angiotensin-(1-12) caused the rapid appearance of both angiotensin I and angiotensin II in the perfusate that peaked between 30 and 60 min of recirculation. Production of angiotensin-(1-7) from exogenous angiotensin-(1-12) rose steadily over the course of the 60-min experiment. These data directly demonstrate that angiotensin-(1-12) is a substrate for the formation of angiotensin peptides in cardiac tissue. This finding further suggests that this angiotensinogen-derived product is a previously unrecognized important precursor peptide to the renin-angiotensin system cascade.
- Published
- 2008
45. Interactions between subtotal nephrectomy and salt: effects on blood pressure and renal function in pregnant and nonpregnant ewes
- Author
-
Karen J. Gibson, Eugenie R. Lumbers, Sarah Chinchen, Amanda C. Boyce, and Clare L. Thomson
- Subjects
medicine.medical_specialty ,Angiotensins ,Physiology ,medicine.medical_treatment ,Pregnancy Complications, Cardiovascular ,Drinking ,Hemodynamics ,Renal function ,Blood Pressure ,Gestational Age ,Kidney ,Nephrectomy ,Hemoglobins ,Diastole ,Heart Rate ,Pregnancy ,Physiology (medical) ,Internal medicine ,Renin ,medicine ,Animals ,Sodium Chloride, Dietary ,Sheep ,business.industry ,Metabolic disorder ,Osmolar Concentration ,Water-Electrolyte Balance ,medicine.disease ,Disease Models, Animal ,Endocrinology ,Blood pressure ,Kidney Tubules ,Hematocrit ,Creatinine ,Hypertension ,Gestation ,Female ,Hypernatremia ,business ,Glomerular Filtration Rate - Abstract
The effects of high salt intake on blood pressure and renal function were studied in nine subtotally nephrectomized pregnant ewes (STNxP) and seven intact pregnant ewes (IntP) in late gestation and in eight subtotally nephrectomized nonpregnant ewes (STNxNP) and seven intact nonpregnant ewes (IntNP). STNxP had higher mean arterial pressures ( P < 0.02) and plasma creatinine levels ( P < 0.001) than IntP. High salt (0.17 M NaCl as drinking water for 5 days) did not change blood pressure in either STNxP or IntP. STNxNP had higher mean arterial pressures ( P = 0.03) and plasma creatinine levels ( P < 0.001) than IntNP. In STNxNP, blood pressure increased with high salt intake and there was a positive relationship between diastolic pressure and sodium balance ( r = 0.497, P = 0.05). This relationship was not present in IntNP, STNxP, or IntP. Because high salt intake did not cause an increase in blood pressure in STNxP, it is concluded that they were protected by pregnancy from further rises in blood pressure. The observed increase in glomerular filtration rate ( P < 0.03) and depression of fractional proximal sodium reabsorption ( P = 0.003) that occurred in STNxP, but not in STNxNP, in response to high salt may have contributed to this protection. As well, the increased production of vasorelaxants in pregnancy may selectively protect against the occurrence of salt-sensitive hypertension in pregnancy.
- Published
- 2008
46. In vitro evidence for an intracellular site of angiotensin action
- Author
-
Richard N. Re, Julia L. Cook, and Zhuo Zhang
- Subjects
Intracellular Fluid ,Intracrine ,medicine.medical_specialty ,Angiotensin receptor ,Angiotensins ,Carcinoma, Hepatocellular ,Physiology ,Angiotensinogen ,Receptors, Cytoplasmic and Nuclear ,Tetrazoles ,Biology ,Peptidyl-Dipeptidase A ,Transfection ,Polymerase Chain Reaction ,Losartan ,chemistry.chemical_compound ,Angiotensin Receptor Antagonists ,Internal medicine ,Renin–angiotensin system ,Renin ,medicine ,Mitotic Index ,Tumor Cells, Cultured ,Animals ,Phenylarsine oxide ,Receptor ,Antihypertensive Agents ,Sequence Deletion ,Receptors, Angiotensin ,Biphenyl Compounds ,Oligonucleotides, Antisense ,Molecular biology ,Angiotensin II ,Recombinant Proteins ,Clone Cells ,Rats ,Alternative Splicing ,Endocrinology ,chemistry ,Bromodeoxyuridine ,Mutagenesis, Site-Directed ,Benzimidazoles ,Cardiology and Cardiovascular Medicine ,hormones, hormone substitutes, and hormone antagonists ,Intracellular ,Cell Division ,medicine.drug - Abstract
To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(−S)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(−S)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33±4.4% ( P −6 mol/L losartan and by 1 μmol/L renin antisense phosphorothioate oligomers but not by 10 −6 mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(−S)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(−S)Exp, while anti–Ang II antibodies have no effect. These results suggest that the Ang(−S)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic.
- Published
- 2001
47. Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors
- Author
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David Z. Levine, George J. Wehbi, Robert M. Carey, Joseph Zimpelmann, and Kevin D. Burns
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Kidney Cortex ,Physiology ,Renal glomerulus ,Kidney Glomerulus ,Down-Regulation ,Peptidyl-Dipeptidase A ,Receptor, Angiotensin, Type 2 ,Receptor, Angiotensin, Type 1 ,Streptozocin ,Nephropathy ,Diabetes Mellitus, Experimental ,Diabetic nephropathy ,Rats, Sprague-Dawley ,Diabetes mellitus ,Internal medicine ,Renin ,Medicine ,Animals ,RNA, Messenger ,Receptor ,Kidney Medulla ,Angiotensin II receptor type 1 ,Receptors, Angiotensin ,business.industry ,medicine.disease ,Angiotensin II ,Anti-Bacterial Agents ,Rats ,Endocrinology ,business ,Kidney disease - Abstract
The interaction of ANG II with intrarenal AT1receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal AT2receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney AT2receptors. Three groups of rats were studied after 2 wk: 1) control (C), 2) streptozotocin (STZ)-induced diabetic (D), and 3) STZ-induced diabetic with insulin implant (D+I), to maintain normoglycemia. By competitive RT-PCR, early diabetes had no significant effect on glomerular mRNA expression for renin, angiotensinogen, or angiotensin-converting enzyme (ACE). In isolated glomeruli, nonglycosylated (41-kDa) AT1receptor protein expression (AT1Aand AT1B) was increased in D rats, with no change in glycosylated (53-kDa) AT1receptor protein or in AT1receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular AT2receptor protein expression (47.0 ± 6.5% of C; P < 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, AT2receptor immunostaining was localized to glomerular endothelial cells and tubular epithelial cells in the cortex, interstitial, and tubular cells in the outer medulla, and inner medullary collecting duct cells. STZ diabetes caused a significant decrease in AT2receptor immunostaining in all kidney regions, an effect partially reversed in D+I rats. In summary, early diabetes has no effect on glomerular mRNA expression for renin, angiotensinogen, or ACE. AT2receptors are present in glomeruli and are downregulated in early diabetes, as are all kidney AT2receptors. Our data suggest that alterations in the balance of kidney AT1and AT2receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy.
- Published
- 2001
48. Plasma aldosterone concentrations are not related to the degree of angiotensin-converting enzyme inhibition in essential hypertensive patients
- Author
-
Takao Saruta, Yoshiyuki Suzuki, Hirotaka Shibata, and Atsuhisa Sato
- Subjects
Male ,medicine.medical_specialty ,Angiotensins ,Physiology ,medicine.drug_class ,Radioimmunoassay ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Pharmacology ,Peptidyl-Dipeptidase A ,Essential hypertension ,Imidazolidines ,chemistry.chemical_compound ,Electrolytes ,Enalapril ,Heart Rate ,Internal medicine ,Renin–angiotensin system ,Renin ,Internal Medicine ,medicine ,Humans ,Aldosterone ,Angiotensin II receptor type 1 ,biology ,business.industry ,Imidazoles ,Angiotensin-converting enzyme ,Middle Aged ,medicine.disease ,Angiotensin II ,Endocrinology ,chemistry ,Mineralocorticoid ,Echocardiography ,ACE inhibitor ,Hypertension ,biology.protein ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,medicine.drug - Abstract
There is increasing evidence of important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Aldosterone plus excess salt administration has been shown to produce both cardiac hypertrophy and cardiac fibrosis in rats. Various clinical studies have reported that aldosterone plays an important role in cardiac hypertrophy; however, the factors that control plasma aldosterone concentrations during angiotensin-converting enzyme (ACE) inhibitor treatment have still not been established. In the present study, we examined the relationship between plasma aldosterone concentrations and the degree of ACE inhibition in 25 essential hypertensive patients treated with an ACE inhibitor. Blood pressure decreased with treatment and plasma ACE activity, estimated in vitro (by a colorimetric method) and in vivo (by plasma angiotensin II/angiotensin I ratio) assay, was suppressed compared with that of hypertensive patients treated with medication other than ACE inhibitors. No relationship was found between the level of ACE inhibition and plasma aldosterone concentrations, which rose in parallel with the duration of ACE inhibitor treatment. The present study demonstrates that continuous ACE inhibitor therapy produces significant suppression of plasma ACE activity in essential hypertensive patients, but that no relationship exists between plasma aldosterone concentrations and levels of ACE inhibition. Plasma aldosterone concentrations tend to increase with the duration of ACE inhibitor treatment, although this increase did not reflect a reduced inhibition of ACE activity.
- Published
- 2000
49. Myocardial renin is neither necessary nor sufficient to initiate or maintain ventricular hypertrophy
- Author
-
John A. Opsahl, Shane E. Wernsing, Juline A. Smith, Stephen A. Katz, Lynn M. Forbis, and Lois Jane Heller
- Subjects
medicine.medical_specialty ,Angiotensins ,Physiology ,Sodium Chloride ,Plasma renin activity ,Losartan ,Renin-Angiotensin System ,Ventricular hypertrophy ,Physiology (medical) ,Internal medicine ,Renin–angiotensin system ,Renin ,medicine ,Animals ,cardiovascular diseases ,Receptor ,Desoxycorticosterone ,Antihypertensive Agents ,Angiotensin II receptor type 1 ,Hypertrophy, Right Ventricular ,business.industry ,Plasma levels ,medicine.disease ,Rats ,Endocrinology ,Cardiac hypertrophy ,Cardiology ,Hypertrophy, Left Ventricular ,business ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,medicine.drug - Abstract
We tested the hypothesis that the myocardial renin-angiotensin system (RAS) is both necessary and sufficient to initiate and maintain all classes of ventricular hypertrophy. Myocardial and plasma renin and angiotensinogen were measured in rats during initiation and maintenance of ventricular hypertrophy associated with DOCA implants and 1% NaCl drinking water, with and without the AT1 ANG II receptor blocker losartan. Additional groups of rats were given a low-sodium diet (0.04%) for 3 wk. Ventricular hypertrophy was initiated within 7 days and maintained for 35 days in DOCA-treated rats despite significantly low myocardial and plasma renin, normal or low myocardial and plasma angiotensinogen, or the presence of losartan. Furthermore, there was no ventricular hypertrophy in low-salt diet-fed animals despite increased myocardial and plasma renin levels and normal angiotensinogen levels. Therefore, the myocardial RAS is not necessary to initiate or maintain cardiac hypertrophy in DOCA-treated rats and is not sufficient to initiate cardiac hypertrophy in low-salt diet-fed rats. Additionally, myocardial renin and angiotensinogen were significantly correlated with corresponding plasma levels.
- Published
- 2000
50. Bi-directional actions of estrogen on the renin-angiotensin system
- Author
-
Ping Li, Carlos M. Ferrario, K.B. Brosnihan, and P.S. Senanayake
- Subjects
Angiotensin receptor ,Physiology ,Vasodilation ,Aorta, Thoracic ,Kidney ,Biochemistry ,angiotensin peptides ,Renin-Angiotensin System ,chemistry.chemical_compound ,Plasma ,Vasoconstrictor Agents ,General Pharmacology, Toxicology and Pharmaceutics ,vasodilation ,lcsh:QH301-705.5 ,angiotensin converting enzyme ,lcsh:R5-920 ,biology ,General Neuroscience ,Estrogen Replacement Therapy ,General Medicine ,Haplorhini ,medicine.anatomical_structure ,hormone replacement ,Ovariectomized rat ,Female ,lcsh:Medicine (General) ,hormones, hormone substitutes, and hormone antagonists ,medicine.medical_specialty ,Angiotensins ,medicine.drug_class ,Ovariectomy ,Immunology ,Biophysics ,Bradykinin ,Peptidyl-Dipeptidase A ,kinins ,nitric oxide ,Internal medicine ,Renin–angiotensin system ,medicine ,Animals ,business.industry ,Angiotensin-converting enzyme ,Estrogens ,Cell Biology ,angiotensin receptors ,Rats ,Endocrinology ,chemistry ,renin ,lcsh:Biology (General) ,Estrogen ,biology.protein ,bradykinin ,business - Abstract
Estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin. We show, however, that angiotensin converting enzyme (ACE) activity in the circulation and in tissues is reduced in two animal models of postmenopausal chronic hormone replacement. We observed a reduction of ACE activity in association with a significant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovariectomized monkeys treated with Premarin (conjugated equine estrogen) replacement for 30 months. Plasma angiotensin II (Ang II) levels were not increased in monkeys treated with estrogen, suggesting that the decrease in ACE curtailed the formation of the peptide. The Ang II/Ang I ratio, an in vivo index of ACE activity, was significantly reduced by estrogen treatment, further supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estrogen replacement treatment for 3 weeks, ACE activity in plasma and tissue (aorta and kidney) and circulating Ang II levels were reduced, whereas circulating levels of angiotensin-(1-7) (Ang-(1-7)) were increased. Ang-(1-7), the N-terminal fragment of Ang II, is a novel vasodilator and antihypertensive peptide. Thus, the net balance of these effects of estrogen on the reninangiotensin vasoconstrictor/vasodilator system is to promote the anti-hypertensive effect.
- Published
- 1999
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