23 results on '"Mangiarua EI"'
Search Results
2. Association of Chairs of Departments of Physiology 2014 Survey Results.
- Author
-
Mangiarua EI and Sturek M
- Subjects
- Budgets organization & administration, Budgets statistics & numerical data, Data Collection, Education, Medical organization & administration, Humans, North America, Education, Medical statistics & numerical data, Ethnicity statistics & numerical data, Faculty, Medical statistics & numerical data, Physiology education, Racial Groups statistics & numerical data, Salaries and Fringe Benefits statistics & numerical data
- Published
- 2015
3. Association of Chairs of Departments of Physiology 2013 Survey Results.
- Author
-
Mangiarua EI and Delamere NA
- Subjects
- Budgets statistics & numerical data, Canada, Data Collection, Faculty statistics & numerical data, Mexico, Physiology education, Puerto Rico, United States, Universities statistics & numerical data, Workforce, Physiology economics, Societies, Scientific, Universities economics
- Published
- 2014
4. MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway.
- Author
-
Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI, and Dasgupta P
- Subjects
- Animals, Cell Proliferation drug effects, Chickens, Down-Regulation drug effects, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Humans, Lung blood supply, Lung cytology, Mice, Mice, Nude, Microvessels cytology, Microvessels drug effects, Models, Biological, Nicotine pharmacology, Nicotinic Antagonists chemistry, Quaternary Ammonium Compounds chemistry, Rats, Stilbenes chemistry, alpha7 Nicotinic Acetylcholine Receptor, Early Growth Response Protein 1 metabolism, Fibroblast Growth Factor 2 metabolism, Neovascularization, Physiologic drug effects, Nicotinic Antagonists pharmacology, Quaternary Ammonium Compounds pharmacology, Receptors, Nicotinic metabolism, Signal Transduction drug effects, Stilbenes pharmacology
- Abstract
Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation of primary human microvascular endothelial cells of the lung (HMEC-Ls). Furthermore, MG624 displayed robust anti-angiogenic activity in the Matrigel, rat aortic ring and rat retinal explant assays. The anti-angiogenic activity of MG624 was assessed by two in vivo models, namely the chicken chorioallantoic membrane model and the nude mice model. In both of these experimental models, MG624 inhibited angiogenesis of human SCLC tumors. Most importantly, the administration of MG624 was not associated with any toxic side effects, lethargy or discomfort in the mice. The anti-angiogenic activity of MG624 was mediated via the suppression of nicotine-induced FGF2 levels in HMEC-Ls. MG624 decreased nicotine-induced early growth response gene 1 (Egr-1) levels in HMEC-Ls, and reduced the levels of Egr-1 on the FGF2 promoter. Consequently, this process decreased FGF2 levels and angiogenesis. Our findings suggest that the anti-angiogenic effects of MG624 could be useful in anti-angiogenic therapy of human SCLCs.
- Published
- 2012
- Full Text
- View/download PDF
5. The short-term consumption of a moderately high-fat diet alters nitric oxide bioavailability in lean female Zucker rats.
- Author
-
Huang K, Huang Y, Frankel J, Addis C, Jaswani L, Wehner PS, Mangiarua EI, and McCumbee WD
- Subjects
- Animals, Biological Availability, Diet, Dietary Fats metabolism, Drinking, Eating, Female, Nitric Oxide blood, Nitric Oxide urine, Rats, Rats, Sprague-Dawley, Rats, Zucker, Reactive Oxygen Species metabolism, Tissue Distribution, Tyrosine analogs & derivatives, Tyrosine metabolism, Dietary Fats administration & dosage, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism
- Abstract
To determine whether short-term consumption of a moderately high-fat diet (MHFD) affects nitric oxide (NO) production, the concentration of stable NO metabolites (NOx) in urine and plasma of rats fed a MHFD (15.6 %g fat) or control diet (4.5 %g fat) was measured weekly for 4 weeks. Plasma and urine NOx levels were significantly depressed in the MHFD group by week 1 and remained so for the duration of the study. Decreased NO bioavailability may result from a decrease in NO production or the scavenging of NO by reactive oxygen species (ROS). Because endothelial NOS (eNOS) is the major contributor to NO production and circulating levels of NOx, eNOS expression was measured in several tissues. At week 1, there was a MHFD-associated decrease in eNOS expression in the liver. Subsequently, eNOS expression declined in the heart and kidney medulla of MHFD-fed rats at weeks 3 and 4, respectively. The expression of eNOS in the kidney cortex and adipose tissue did not change. These results suggest that a MHFD alters eNOS expression in a time-dependent and tissue-specific manner. In the liver, NOS activity and tissue levels of NOx and nitrotyrosine were measured. Nitrotyrosine levels were used as an indirect measure of the NO scavenged by ROS. There was a decrease in NOS activity, suggesting that the low levels of hepatic NOx were due, in part, to a decrease in NO production. In addition, there was a dramatic increase in nitrotyrosine formation, suggesting that the decline in hepatic NOx was also due to an increased interaction of NO with ROS. Tyrosine nitration commonly has detrimental effects on proteins. The decrease in NO and increase in protein nitration could potentially have adverse effects on tissue function.
- Published
- 2011
- Full Text
- View/download PDF
6. Acetaminophen protects against iron-induced cardiac damage in gerbils.
- Author
-
Walker EM Jr, Epling CP, Parris C, Cansino S, Ghosh P, Desai DH, Morrison RG, Wright GL, Wehner P, Mangiarua EI, Walker SM, and Blough ER
- Subjects
- Acetaminophen administration & dosage, Acetaminophen metabolism, Administration, Oral, Analysis of Variance, Animals, Body Weight, Echocardiography, Gerbillinae, Heart Diseases pathology, Injections, Intraperitoneal, Liver metabolism, Liver pathology, Male, Myocardium pathology, Organ Size, Specific Pathogen-Free Organisms, Spectrophotometry, Atomic, Acetaminophen therapeutic use, Heart Diseases etiology, Heart Diseases prevention & control, Iron metabolism, Iron Overload complications
- Abstract
There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.
- Published
- 2007
7. A moderately high fat diet promotes salt-sensitive hypertension in obese zucker rats by impairing nitric oxide production.
- Author
-
Morrison RG, Mills C, Moran AL, Walton CE, Sadek MH, Mangiarua EI, Wehner PS, and McCumbee WD
- Subjects
- Animals, Body Weight, Diet adverse effects, Disease Models, Animal, Feedback, Physiological, Female, Insulin blood, Leptin blood, Nitrates metabolism, Nitrates urine, Nitric Oxide urine, Nitric Oxide Synthase biosynthesis, Nitrites metabolism, Nitrites urine, Nutrition Disorders complications, Nutrition Disorders metabolism, Obesity complications, Rats, Rats, Zucker, Dietary Fats adverse effects, Hypertension etiology, Hypertension metabolism, Nitric Oxide deficiency, Obesity metabolism, Sodium Chloride, Dietary adverse effects
- Abstract
The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.
- Published
- 2007
- Full Text
- View/download PDF
8. Age-associated changes in hearts of male Fischer 344/Brown Norway F1 rats.
- Author
-
Walker EM Jr, Nillas MS, Mangiarua EI, Cansino S, Morrison RG, Perdue RR, Triest WE, Wright GL, Studeny M, Wehner P, Rice KM, and Blough ER
- Subjects
- Animals, Arrhythmias, Cardiac pathology, Arrhythmias, Cardiac physiopathology, Disease Models, Animal, Echocardiography methods, Heart Diseases physiopathology, Heart Ventricles physiopathology, Hypertrophy, Left Ventricular pathology, Hypertrophy, Left Ventricular physiopathology, Male, Organ Size, Rats, Rats, Inbred BN, Rats, Inbred F344, Ventricular Dysfunction, Left pathology, Ventricular Dysfunction, Left physiopathology, Aging physiology, Heart physiopathology, Heart Diseases pathology, Heart Ventricles pathology, Myocardium pathology
- Abstract
Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other recordings from parasternal long- and short-axis views were obtained using a Phillips 5500 ECHO system with a 12 megahertz transducer. Hearts and aortas from sacrificed rats were evaluated grossly and microscopically. The ECHO studies revealed persistent cardiac arrhythmias (chiefly PVCs) in 72% (13/18) of 36-mo rats, 10% (1/10) of 30-mo rats, and none in 6-mo rats (0/16). Gross and microscopic studies showed left ventricular (LV) dilatation, borderline to mild hypertrophy, and areas of fibrosis that were common in 36-mo rats, less evident in 30-mo rats, and absent in 6-mo rats. Aging was associated with mild to moderate decreases of LV diastolic and systolic function. Thus, male F344/BN F1 rats demonstrated progressive age-related (a) decline in cardiac function (diastolic and systolic indices), (b) LV structural changes (chamber dimensions, volumes, and wall thicknesses), and (c) persistent arrhythmias. These changes are consistent with those in humans. The noninvasive ECHO technique offers a means to monitor serial age-related cardiac failure and therapeutic responses in the same rats over designated time intervals.
- Published
- 2006
9. Progression of renal damage in the obese Zucker rat in response to deoxycorticosterone acetate-salt-induced hypertension.
- Author
-
Morrison RG, Carpenter AB, Adams VL, Mangiarua EI, Wehner PS, and McCumbee WD
- Subjects
- Animals, Blood Pressure drug effects, Body Weight, Disease Progression, Diuresis drug effects, Drinking Behavior, Feeding Behavior, Female, Hypertension pathology, Hypertension physiopathology, Kidney Diseases pathology, Rats, Rats, Zucker, Desoxycorticosterone, Hypertension chemically induced, Kidney Diseases physiopathology, Obesity genetics, Obesity pathology
- Abstract
This study assessed the progression of renal damage in obese Zucker rats in response to deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Renal damage was evaluated by light microscopy and urine analysis at weekly intervals during the developmental phase of DOCA-salt hypertension and once during the plateau phase 42 days after the onset of treatment. Decreased tubular function was evident by day 8, as indicated by a significant increase in urine N-acetyl-beta-D-glucosaminidase activity and glucose excretion. The tubular index, a measure of tubular damage, was significantly elevated by day 15 and continued to increase throughout the experiment. Glomerular damage, which was evident by day 8, was followed by increased urine albumin excretion by day 15. Only a few sclerotic renal glomeruli were apparent before the plateau phase; however, by day 42, approximately 50% of the glomeruli were sclerotic. Hyperplastic vascular changes were mild at day 8 and slowly increased in severity during the developmental phase. By day 42 the vascular changes were severe with some vessels so hyperplastic that their lumens were almost occluded. These findings show progressive changes in renal structure and function that begin as early as day 8 and increase progressively until severe changes are present at day 42, resulting in an end-stage
- Published
- 2005
10. Increased sensitivity of the obese Zucker rat to deoxycorticosterone-salt-induced hypertension.
- Author
-
Morrison RG, Carpenter AB, Moore SK, Mangiarua EI, Valentovic MA, Walker EM Jr, Wehner PS, Rhoten WB, Touchon RC, and McCumbee WD
- Subjects
- Animals, Blood Pressure, Disease Models, Animal, Disease Susceptibility epidemiology, Female, Hypertension, Renal pathology, Kidney Glomerulus pathology, Nephrectomy, Rats, Rats, Zucker, Risk Factors, Desoxycorticosterone, Hypertension, Renal chemically induced, Hypertension, Renal epidemiology, Obesity epidemiology, Sodium Chloride, Dietary
- Abstract
Objective: The objective of this study was to test the hypothesis that obesity increases the sensitivity of rats to experimentally induced hypertension., Design and Methods: To induce hypertension, unilaterally nephrectomized lean and obese Zucker rats were injected with 25 mg/kg of deoxycorticosterone acetate (DOCA) twice weekly for 5 weeks and given water containing 1% NaCl to drink. Unilaterally nephrectomized control rats were injected with vehicle and drank tap water. Systolic blood pressure (SBP) was measured by the tail cuff method. Renal histology and urinary albumin excretion were used to assess the effects of the experimental treatment on the kidney., Results: Obese rats exhibited a significant rise in SBP at 4 days after the start of DOCA-salt treatment. In contrast, SBP of DOCA-treated lean rats was not significantly elevated from pretreatment measurements until day 22. Moreover, SBP was significantly higher during the plateau phase of blood pressure development in obese DOCA-salt treated rats (196 mmHg) than in correspondingly treated lean rats (150 mmHg). Both obesity and DOCA-salt treatment promoted glomerulosclerosis and mild tubulointerstitial damage in the kidney with DOCA-salt treatment exacerbating the effect of obesity. Urinary albumin excretion was significantly greater in obese control rats compared with lean controls and in DOCA-treated obese rats relative to vehicle-treated obese rats., Conclusion: Results of this study indicate that obese Zucker rats are more sensitive to mineralocorticoid-induced hypertension than lean rats. This study provides experimental evidence supporting the epidemiological findings that obesity is a risk factor for the development of hypertension.
- Published
- 2002
- Full Text
- View/download PDF
11. Angiotensin II-induced growth effects in vascular smooth muscle in cell culture and in the aortic tunica media in organ culture.
- Author
-
Mangiarua EI, Galagedera NJ, and Eastham LL
- Subjects
- Animals, Aorta, Thoracic, Cell Division drug effects, Cells, Cultured, DNA biosynthesis, Male, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular metabolism, Organ Culture Techniques, Phenotype, Proline metabolism, Rats, Rats, Sprague-Dawley, Thymidine metabolism, Tunica Media drug effects, Tunica Media metabolism, Angiotensin II pharmacology, Muscle, Smooth, Vascular cytology, Tunica Media cytology, Vasoconstrictor Agents pharmacology
- Abstract
Several different studies have investigated the growth effects of angiotensin II on vascular smooth muscle cells in culture. However, smooth muscle cells change their phenotype when placed in culture. The objective of the present study was to investigate the effects of angiotensin II on (3)H-thymidine and (3)H-proline incorporation in vascular smooth muscle cells in culture and in the tunica media of blood vessels perfused at normal physiological pressures in organ culture, thus avoiding the phenotypic changes observed in cell culture. The perfusion system consisted of a peristaltic pump and a closed circuit of plastic tubing connected to a culture media bottle where thoracic rat aortae were placed. Angiotensin II induced an increase in (3)H-thymidine and (3)H-proline incorporation in both culture systems. The results suggest that angiotensin II may play a role in mediating cell growth in vascular smooth muscle cells in their 'contractile' as well as in their 'synthetic' phenotype.
- Published
- 2001
- Full Text
- View/download PDF
12. Platelet-derived growth factor mediates angiotensin II-induced DNA synthesis in vascular smooth muscle cells.
- Author
-
Mangiarua EI, Palmer VL, Lloyd LL, and McCumbee WD
- Subjects
- Animals, Cell Division, Cells, Cultured, Male, Rats, Rats, Sprague-Dawley, Angiotensin II metabolism, DNA Replication, Muscle, Smooth, Vascular metabolism, Platelet-Derived Growth Factor metabolism
- Abstract
In order to elucidate the mechanism of angiotensin II (ANG II)-induced proliferation in vascular smooth muscle cells in culture, growth rates and 3H-thymidine incorporation into DNA in response to ANG II treatment were examined in cultured rat aortic smooth muscle cells. ANG II-treated and control cells were exposed to the ANG II receptor antagonists [Sar1, Val5, Ala8]-ANG II (Sar) and DUP753 and to antibody against platelet-derived growth factor (PDGF). In growing cells, ANG II acted as a moderate mitogen, inducing an increase in growth rate during the first two days of treatment. ANG II induced a marked increase in 3H-thymidine incorporation in cultured vascular smooth muscle cells. The effect was blocked by the ANG II inhibitors Sar and DUP753 and by the PDGF antibody. ANG II was able to stimulate vascular smooth muscle growth in cell culture. The effect seemed to be mediated, at least in part, by PDGF. These results are in agreement with a possible role of ANG II in promoting vascular growth in physiological and/or pathological situations.
- Published
- 1997
- Full Text
- View/download PDF
13. Increased intraluminal pressure induces DNA synthesis and c-fos expression in perfused rat aorta.
- Author
-
Mangiarua EI, Galagedera NJ, and Patterson JR
- Subjects
- Animals, Aorta cytology, Aorta metabolism, Blotting, Northern, Cell Division, Glyceraldehyde-3-Phosphate Dehydrogenases genetics, Glyceraldehyde-3-Phosphate Dehydrogenases metabolism, Hemodynamics, Male, Osmolar Concentration, Perfusion, Pressure, Rats, Rats, Sprague-Dawley, Thymidine metabolism, DNA Replication, Gene Expression Regulation, Genes, fos genetics, Muscle, Smooth, Vascular cytology
- Abstract
The molecular mechanisms responsible for the vascular hypertrophy observed in the arteries of hypertensive subjects are poorly understood. In this study, we tested the hypothesis that an increase in intraluminal pressure could by itself induce some of the vascular changes associated with hypertension, such as increased DNA synthesis and c-fos expression. We perfused rat thoracic aortae at different pressures for up to 4 h. The perfusion system consisted of a peristaltic pump and a closed circuit of plastic tubing connected to a culture media bottle where rat thoracic aortae were placed. After a 30 min equilibration period at 20 mm Hg, the perfusion pressure was adjusted to "normotensive levels" (132 +/- 3/59 +/- 4 mm Hg) or "hypertensive levels" (204 +/- 5/74 +/- 8 mm Hg). 3H-Thymidine was added at this time. After 4 h, the arteries were removed from the apparatus. Tunica media and adventitia were separated and processed for scintillation counting. 3H-Thymidine incorporation was 39% higher in the "hypertensive" than in the "normotensive" arteries. In separate experiments, after a 20 min equilibration period, the arteries were perfused for an additional 30 min at 50/10, 100/35, or 150/50 mm Hg. After being removed from the perfusion apparatus, the arteries were homogenized and total RNA was isolated. c-fos Expression was analyzed by Northern blot. c-fos Expression corresponded directly with the perfusion pressure. The highest levels of c-fos expression were detected in the arteries exposed to the highest pressures. These findings support the hypothesis that hemodynamic and/or mechanical factors can influence cell growth and function.
- Published
- 1996
- Full Text
- View/download PDF
14. Interactions between angiotensin II and adenosine 3':5'-cyclic monophosphate in the regulation of amino acid transport by vascular smooth muscle cells.
- Author
-
McCumbee WD, Hickey VL, Lloyd LL, and Mangiarua EI
- Subjects
- 1-Methyl-3-isobutylxanthine pharmacology, Animals, Aorta drug effects, Aorta metabolism, Biological Transport, Drug Interactions, In Vitro Techniques, Male, Muscle, Smooth, Vascular metabolism, Phorbol 12,13-Dibutyrate pharmacology, Phosphodiesterase Inhibitors pharmacology, Rats, Rats, Sprague-Dawley, Aminoisobutyric Acids metabolism, Angiotensin II pharmacology, Cyclic AMP pharmacology, Muscle, Smooth, Vascular drug effects
- Abstract
The regulation of amino acid transport by angiotensin II (AII) and cyclic AMP (cAMP) was assessed in cultured vascular smooth muscle cells, using a nonmetabolizable amino acid, alpha-[3H]aminoisobutyric acid (AIB). An exposure time in excess of 2 h was required for AII to elicit a stimulatory response, the magnitude of which increased in a time-dependent manner for 12 h. AII-induced transport was blocked by [1-sarcosine, 8-isoleucine]AII, a competitive inhibitor of AII binding. The effect of AII was not abolished by downregulation protein kinase C with phorbol 12,13-dibutyrate or by use of a protein kinase C inhibitor, suggesting that transport in response to AII can be mediated by a protein kinase C independent pathway. In contrast, the elimination of calcium from the incubation medium reduced AII-stimulated AIB uptake. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide partially inhibited AIB uptake in response to AII, suggesting that calmodulin may be involved in the modulation of AII-stimulated amino acid transport. AIB transport was also increased by elevating intracellular cAMP levels via beta-adrenergic receptor stimulation, the use of a cAMP analog (N6-monobutyryl cAMP), or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) or by direct stimulation of adenylate cyclase with forskolin. cAMP-induced AIB transport was evident within 10 min and peaked within 1 h. At 1 h AII enhanced cAMP-stimulated AIB transport. A possible mechanism for this effect is suggested by the observation that AII potentiated cAMP production in response to isoproterenol and 3-isobutyl-1-methylxanthine.
- Published
- 1996
15. Morphometric study of cerebral arteries from spontaneously hypertensive and stroke-prone spontaneously hypertensive rats.
- Author
-
Mangiarua EI and Lee RM
- Subjects
- Animals, Blood Pressure, Cerebral Arteries innervation, Cerebrovascular Disorders physiopathology, Hypertension physiopathology, Linear Models, Male, Rats, Rats, Inbred WKY, Sympathectomy, Chemical, Sympathetic Nervous System, Cerebral Arteries anatomy & histology, Cerebrovascular Disorders pathology, Hypertension pathology, Rats, Inbred SHR anatomy & histology
- Abstract
Objective: The importance of sympathetic innervation for the development of structural changes in the cerebral arteries of hypertensive animals was studied., Design: Sympathetic denervation was induced with combined treatment from birth of antibody against nerve growth factor and guanethidine. Previous studies from our laboratory showed that this procedure not only caused a permanent denervation of the mesenteric arteries, but also prevented the development of hypertension in spontaneously hypertensive rats (SHR)., Methods: Morphometric measurement of the structural changes was carried out in the basilar, superior cerebellar, posterior cerebral and middle cerebral arteries from 28-week-old SHR, stroke-prone SHR, and normotensive Wistar-Kyoto rats. The results were compared with those obtained from cerebral arteries of sympathectomized rats., Results: Total vascular wall cross-sectional area was significantly larger in the basilar and superior cerebellar arteries from hypertensive rats compared with normotensives. The change was characterized by an increase in the number of smooth muscle cell layers. There were also differences between the two hypertensive groups in some arteries. Sympathetic denervation attenuated the development of hypertension and vascular changes in some arteries. There was a positive linear correlation between blood pressure and medial cross-sectional area, and between blood pressure and the number of smooth muscle cell layers for the four arteries analysed., Conclusion: Sympathetic nerves have a trophic influence upon the remodelling of some cerebral arteries during the development of genetic hypertension.
- Published
- 1992
- Full Text
- View/download PDF
16. Morphological and contractile characteristics of rat aortae perfused for 3 or 6 days in vitro.
- Author
-
Mangiarua EI, Moss N, Lemke SM, McCumbee WD, Szarek JL, and Gruetter CA
- Subjects
- Acetylcholine pharmacology, Angiotensin II pharmacology, Animals, Aorta, Thoracic cytology, Aorta, Thoracic drug effects, In Vitro Techniques, Isoproterenol pharmacology, Kinetics, Male, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects, Nitroprusside pharmacology, Perfusion instrumentation, Perfusion methods, Potassium pharmacology, Rats, Rats, Inbred Strains, Serotonin pharmacology, Time Factors, Aorta, Thoracic physiology, Isometric Contraction drug effects, Muscle, Smooth, Vascular physiology
- Abstract
We studied the morphological and contractile characteristics of rat thoracic aortic segments perfused for 3 or 6 days under pulsatile conditions. Light microscopic examination of the segments revealed the presence of an unchanged tunica media. However, the intimal surface was mostly devoid of endothelial cells. The perfused aortic segments showed a dramatic increase in spontaneous tone when compared to fresh and sham-treated aortic segments. Maximum responses to potassium and norepinephrine were reduced after 3 days of perfusion (20-40% reduction), while maximum responses to 5-hydroxytryptamine and angiotensin II were not significantly different. After 6 days of perfusion, maximum responses to all agonist were reduced (50-60%). Sensitivity to norepinephrine was not affected by the treatment, while sensitivity to 5-hydroxytryptamine was reduced. The perfused aortic segments relaxed well in response to isoproterenol. Our system provides a useful experimental model for short-term studies of hypertension- and atherosclerosis-related vascular changes. Further refinement and characterization could improve the performance of the system for longer-term studies.
- Published
- 1992
17. Hypertensive factor in different models of experimental hypertension.
- Author
-
Mangiarua EI, Wright GL, Rankin GO, and McCumbee WD
- Subjects
- Animals, Aorta drug effects, Aorta metabolism, Blood Pressure, Calcium metabolism, Desoxycorticosterone, Hypertension chemically induced, Hypertension, Renovascular physiopathology, Male, Peptides blood, Rats, Rats, Inbred SHR, Rats, Inbred Strains, Rats, Inbred WKY, Hypertension physiopathology, Peptides pharmacology
- Abstract
A hypertensive factor (HF), isolated from rat erythrocytes, has been shown to stimulate in vitro calcium uptake in aortic rings and to elevate blood pressure when injected into normotensive rats. In the present study, we investigated tissue responsiveness to HF in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), 2-kidney, 1-clip renovascular hypertensive rats and uninephrectomized rats that were given water or saline to drink or that were treated with DOCA and given water or saline to drink (DOCA-salt). Tissue responsiveness was determined by incubating aortic rings from the rats in the different groups with a constant amount of HF and measuring "lanthanum-resistant" calcium uptake. Tissue sensitivity to HF was greater in SHR than in WKY. In contrast, tissue sensitivity to HF was not enhanced in 2-kidney, 1-clip renovascular and DOCA-salt hypertensive rats relative to their appropriate controls. These results suggest that the increased tissue responsiveness to HF found in SHR is not universally associated with elevated blood pressure; increased tissue sensitivity seems to be a specific characteristic of genetic hypertension.
- Published
- 1991
- Full Text
- View/download PDF
18. Effects of cyclic adenosine 3',5'-monophosphate on amino acid transport and incorporation into protein in the rat aorta.
- Author
-
McCumbee WD and Mangiarua EI
- Subjects
- 1-Methyl-3-isobutylxanthine pharmacology, Aminoisobutyric Acids pharmacology, Animals, Aorta, Thoracic drug effects, Bucladesine analogs & derivatives, Bucladesine pharmacology, Extracellular Space drug effects, Extracellular Space metabolism, In Vitro Techniques, Male, Rats, Rats, Inbred Strains, Amino Acids metabolism, Aorta, Thoracic metabolism, Cyclic AMP pharmacology, Muscle Proteins biosynthesis
- Abstract
To assess the effects of cyclic AMP on amino acid transport and incorporation into aortic tissue protein, rat aortic rings were incubated with the cyclic AMP analog, N6-monobutyryl cyclic AMP (MBcAMP), the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (MIX), and radiolabeled amino acids. Subsequently, the aortic rings were homogenized in 5% trichloroacetic acid (TCA) and processed for liquid scintillation counting. Radioactivity present in the TCA supernatant following centrifugation was used to estimate amino acid transport. TCA-precipitable radioactivity was used as a measure of amino acid incorporation into protein. MBcAMP induced an increase in the uptake of [3H]alpha-aminoisobutyric acid into aortic rings and an increase in the incorporation of radiolabeled proline and leucine into TCA-precipitable protein. Similar effects were observed with low concentrations of MIX (0.025-0.25 mM); however, at higher concentrations of MIX, there was an attenuation of the effect or frank inhibition. Maximum stimulation of transport was observed within 90-120 min of the addition of MIX or MBcAMP to the incubation medium, whereas the effect on amino acid incorporation was not detectable until after 12 h of exposure to MIX or MBcAMP. The effects of cyclic AMP on transport were observed in both the tunica media and the tunica adventitia, whereas the effects on amino acid incorporation into protein were observed only in the tunica media. These data are consistent with a possible role for cyclic AMP in promoting changes in the tunica media that could lead to the development of vascular hypertrophy.
- Published
- 1991
- Full Text
- View/download PDF
19. Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats.
- Author
-
Mangiarua EI and Lee RM
- Subjects
- Aging physiology, Animals, Blood Pressure, Body Weight, Female, Fluorescence, Male, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Cerebral Arteries innervation, Hypertension physiopathology, Mesenteric Arteries innervation, Sympathetic Nervous System physiopathology
- Abstract
The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure.
- Published
- 1990
- Full Text
- View/download PDF
20. Effect of dietary calcium on in vitro aortic tissue responsiveness to a hypertensive factor.
- Author
-
Mangiarua EI, Wright GL, and McCumbee WD
- Subjects
- Animals, Aorta drug effects, Blood Pressure drug effects, Body Weight drug effects, Calcium metabolism, Eating drug effects, Homeostasis, Male, Phosphates metabolism, Rats blood, Rats, Inbred SHR, Rats, Inbred WKY, Tissue Extracts pharmacology, Aorta physiology, Calcium, Dietary pharmacology, Erythrocytes metabolism, Hypertension metabolism
- Abstract
It has been proposed that calcium supplementation in the diet is associated with a reduction in blood pressure. In the present study, we investigated vascular tissue sensitivity to a hypertensive factor (HF) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high calcium diet, a low calcium diet and a food restricted diet. HF, which has been isolated from erythrocytes, increases blood pressure when injected into normotensive rats and stimulates calcium uptake by aortic rings in vitro. Five-week-old rats were divided into the following groups: SHR and WKY fed a regular diet (1% calcium), SHR and WKY fed a high calcium diet (4% calcium), SHR and WKY fed a low calcium diet (0.02% calcium) and SHR and WKY fed a regular diet (1% calcium) in which food intake was restricted to 65% of ad libitum intake. Food intake, body weight, urine phosphate excretion and blood pressure development were followed for 8 weeks. At sacrifice, plasma levels of calcium and phosphate were determined. Tissue responsiveness to HF was calculated by incubating aortic rings from the rats in the different groups with HF and measuring lanthanum-resistant calcium uptake. A 4-fold increase in dietary calcium reduced blood pressure and tissue responsiveness to HF in SHR. Neither parameter was affected by the high calcium diet in WKY. The low calcium diet had no effect on either blood pressure or tissue responsiveness to HF in SHR or WKY. Restriction of food intake induced a reduction in blood pressure and in tissue responsiveness to HF in SHR. It did not affect the same parameters in WKY. The results suggest that the increased tissue responsiveness to HF in the SHR may be associated with high blood pressure.
- Published
- 1990
- Full Text
- View/download PDF
21. Denervation increases myogenic tone in a resistance artery in the growing rabbit ear.
- Author
-
Mangiarua EI, Joyce EH, and Bevan RD
- Subjects
- Animals, Arteries anatomy & histology, Arteries drug effects, Arteries physiology, Ear growth & development, Male, Norepinephrine pharmacology, Papaverine pharmacology, Rabbits, Ear blood supply, Muscle Contraction drug effects, Sympathectomy, Vascular Resistance
- Abstract
The effect of chronic sympathetic and sensory denervation of the growing rabbit ear vasculature on myogenic tone in a resistance artery was studied. Unilateral superior cervical ganglionectomy and section of greater and anterior auricular nerves were performed at 4 wk of age. Compared with the contralateral control, 2 and 6 wk later, the denervated artery developed greater stretch-dependent myogenic tone. This phenomenon may partially account for the return of tone described in the denervated ear vasculature.
- Published
- 1986
- Full Text
- View/download PDF
22. Aortic cyclic AMP levels in hypertensive rats.
- Author
-
Mangiarua EI, Wright GL, and McCumbee WD
- Subjects
- Animals, Desoxycorticosterone, Hypertension chemically induced, Male, Rats, Rats, Inbred Strains, Sodium Chloride, Aorta metabolism, Cyclic AMP metabolism, Hypertension metabolism, Hypertension, Renovascular metabolism
- Abstract
The levels of adenosine 3':5' cyclic monophosphate (cyclic AMP) were measured in aortae from 2-kidney, 1-clip renovascular hypertensive and DOCA-salt hypertensive rats. Cyclic AMP concentration and content were increased in the arteries from the hypertensive animals compared to their normotensive controls. There was a significant positive linear correlation between aortic cyclic AMP concentration and blood pressure and between aortic cyclic AMP content and blood pressure. Since cyclic AMP has been shown to be involved in cellular proliferation and protein synthesis, a perturbation in the normal functioning of this second messenger system could be related to some of the vascular changes associated with the hypertensive process.
- Published
- 1989
- Full Text
- View/download PDF
23. Altered endothelium-mediated relaxation after denervation of growing rabbit ear artery.
- Author
-
Mangiarua EI and Bevan RD
- Subjects
- Animals, Arteries innervation, Ear, External blood supply, Endothelium physiology, Male, Methacholine Chloride, Methacholine Compounds pharmacology, Muscle Relaxation, Muscle, Smooth, Vascular physiology, Nitroprusside pharmacology, Rabbits, Receptors, Muscarinic pharmacology, Time Factors, Arteries physiology, Muscle, Smooth, Vascular innervation
- Abstract
The relaxation response to methacholine and sodium nitroprusside was examined in ring segments from the posterior auricular artery and its continuation the central ear artery in growing rabbits 2, 4, 6 and 8 weeks following unilateral adrenergic and sensory denervation. The maximal relaxation achieved by methacholine (endothelium-dependent) was significantly depressed in the denervated arteries compared with the contralateral controls. Sodium nitroprusside (endothelium-independent relaxant agent) elicited the maximal relaxation in all tissues. These results demonstrated impaired arterial endothelium-dependent relaxation to methacholine after chronic denervation.
- Published
- 1986
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.