Search

Background African ancestry patients are considered separately in hypertension guidelines because of more severe hypertension that is presumably harder to control. However, despite the perceived benefit in reducing health disparities, racial profiling in medicine is increasingly criticized for its potential of bias and stereotyping. Therefore, we studied whether creatine kinase (CK), an ATP-regenerating enzyme that enhances vascular contractility and sodium retention, could serve as a more proximate causal parameter of therapy failure than race/ancestry. Methods In a random multiethnic population sample, we compared the performance of African ancestry vs. resting plasma CK as predictors of treated uncontrolled hypertension. Difference in area under the receiver operating curve (AUC) was the primary outcome. Results We analyzed 1,405 persons of African, Asian, and European ancestry (40.2% men, mean age 45.5 years, SE 0.2). Hypertension prevalence was 39% in African vs. 29% in non-African ancestry participants vs. 41% and 27% by high and low CK tertiles. Control rates of treated patients were similar by ancestry (African ancestry patients 40%, non-African ancestry 41%; P = 0.84), but 27% vs. 53% in patients with high vs. low CK (22% vs. 67% in African and 32% vs. 52% in non-African participants). AUC was 0.51 [0.41–0.60] for African ancestry vs. 0.64 [0.55–0.73] for log CK (P = 0.02). Conclusions In contrast to African ancestry, CK might identify hypertensive patients at risk for therapy failure across different ancestry groups. Larger, prospective studies should establish whether resting plasma CK is clinically useful as an impartial method to help predict antihypertensive therapy failure.

Background The gut‐derived hormone GLP‐1 (glucagon‐like peptide‐1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP‐1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP‐1‐mediated diuresis and natriuresis in high‐fat diet (HFD)‐induced obese rats. Methods and Results Obesity was induced in rats by HFD for 12 weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP‐1R (GLP‐1 receptor) agonist exendin‐4 were monitored in anesthetized control and HFD rats. Renal GLP‐1R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP‐1R and neprilysin in kidney epithelial LLC‐PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin‐4 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40 minutes, 387±32 versus 650±65 µL/gkw; cumulative sodium excretion at 40 minutes, 42±5 versus 75±10 µEq/gkw, P P Conclusions These results suggest that renal sympathetic nerve activation contributes to the blunted diuretic and natriuretic effects of GLP‐1 in HFD obese rats. This study provides significant novel insight into the potential renal nerve–neprilysin–GLP‐1 pathway involved in renal dysfunction during obesity that leads to hypertension.

Tissue sodium content byPatients with T2DM were compared to those with primary hypertension. Patients with T2DM were off any antidiabetic and hypertensive patients off any antihypertensive therapy for at least 4 weeks. Skin and muscle sodium content was assessed non-invasively with a 3.0 T clinical MRI system (Magnetom Verio, Siemens Health Care, Erlangen, Germany) in each patient.In patients with T2DM (N = 59) we observed significantly greater muscle sodium content (diabetes: 20.6 ± 3.5 vs hypertension: 16.3 ± 2.5 mmol/l, p 0.001) and skin sodium content (diabetes: 24.5 ± 7.2 vs hypertension: 20.6 ± 5.7 mmol/l, p = 0.01) than in those with primary hypertension (N = 33). When potential confounders (age, body mass index, gender, systolic and diastolic blood pressure, estimated glomerular filtration rate) were entered in a covariance analysis, both skin sodium content (p = 0.037) and muscle sodium content (p 0.001) were still clearly elevated.Patients with T2DM have greater skin and muscle sodium content. These are the first known data to demonstrate increased tissue sodium content in patients with T2DM, measured by

Arterial hypertension remains the world's leading mortality risk factor and despite overwhelming evidence that blood pressure-lowering strategies greatly reduce the cardiovascular risk, a substantial proportion of hypertensive individuals worldwide fail to achieve an optimal blood pressure control under treatment. Among the causes responsible for the gap existing between blood pressure lowering potential of the different antihypertensive treatments and real-life practice is the presence of drug-induced hypertension. Many therapeutic agents or substances may directly favour an increment of blood pressure values or counteract the blood pressure lowering effects of antihypertensive drugs. Excessive water and sodium retention, direct vasoconstriction or sympathomimetic activation are major mechanisms of action of such substances. The present manuscript will review medications and other substances that may increase blood pressure, also suggesting the choice of the more appropriate antihypertensive agents to employ when withdrawal of the substance or drug causing an elevation of blood pressure values is not possible.

Objective: Vasopressin increases water permeability and activity of the epithelial sodium channel ENaC in the distal nephron of the kidney, favoring increased water and sodium retention. We hypothesized that genetically mediated differences in circulating vasopressin concentrations could contribute to features of hypertension that vary between non-Hispanic blacks and whites. To test this hypothesis we measured copeptin, a fragment of pre-pro arginine vasopressin with a prolonged half-life that is more easily quantified. Methods: The Genetic Epidemiology of Responses to Antihypertensives (GERA) I study was designed to identify predictors of response to diuretic therapy in non-Hispanic black and non-Hispanic white adults with essential hypertension. Blood samples were obtained after a 4 week washout of anti-hypertensive medication while on a sodium intake of 2 mmol/kg. Copeptin was measured from thawed EDTA plasma samples using the copeptin proAVP homogeneous automated immunofluorescent assay on the BRAHMS Kryptor Compact PLUS (Thermo Fisher). Results: Copeptin was significantly higher in blacks (median: 7.4 pmol/L, IQR: 4.4-10.2 pmol/L) than in whites (median: 5.4 pmol/L, IQR: 3.6-8.0 pmol/L) (p Conclusions: Higher copeptin (vasopressin) concentrations in non-Hispanic blacks compared to whites may contribute to the distinct differences in the hypertensive phenotypes between these racial groups. The underlying mechanism(s) require further study.

Metformin is the first-line drug in the treatment of type 2 diabetes mellitus. The aim of this work was to evaluate the efficacy of metformin treatment in reducing blood pressure and investigate the molecular mechanism using a preclinical animal model. Adult male and female diabetic db/db mice with a blood glucose of greater than 300 mg/dl were salt-loaded (8% NaCl) for 10 days to induce hypertension. The mice were subject to metabolic cage studies for 24 hour urine collections in order to measure urinary electrolytes, albumin, and creatinine. Blood pressure was measured weekly by the tail-cuff method to assess the effect of metformin or vehicle given by oral gavage (dose of 60 mg/kg of body weight per day). At the end of the study the mice was euthanized and the left kidney was formalin-fixed and paraffin-embedded for immunohistochemistry while the right kidney was homogenized for Western blotting. Western blotting showed attenuation of total NCC and phospho-NCC in diabetic db/db mice given an oral gavage of metformin (Pearson correlation coefficient: 0.9470 +/- 2.52e-3) compared to vehicle (Pearson correlation coefficient: 0.9800 +/- 2.86e-3). Immunohistochemical analysis showed less co-localization of the actin cytoskeleton protein filamin and phosphorylated NCC in the metformin treated group compared to the control group. Taken together, we show metformin decreases sodium retention and blood pressure by reducing the density of renal NCC at the luminal membrane and the association between NCC and the actin cytoskeleton.

This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms. The premonitory symptoms of migraine include food cravings for salty foods, which can alleviate migraine pain. Edema, possibly related to large amounts of salt consumed in binge eating, can cause approximately four pounds of retained fluid. This amount of fluid is similar to the fluid retained before the onset of migraine headache, which may be accompanied by polyuria. This paper proposes that inhibited withdrawal from highly processed food intake, rich in salt, mediates an association between increased sodium chloride intake and relief from migraine headache pain. The relief from withdrawal symptoms could also be a mediating factor that explains the controversial findings inversely associating dietary sodium intake with migraine history. Moreover, the withdrawal of retained sodium and edema related to the use of nonsteroidal anti-inflammatory drugs may elucidate a potential mechanism in medication overuse headache. Further research is needed to investigate the pain experienced from sodium chloride withdrawal in migraine headache.

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the treatment of hypertension with different antihypertensive drugs inducing a comparable blood pressure reduction but different effects for example on oxidative stress and oxidative stress related proteins and/or Rho kinase and sodium retention, could be helpful for the choice of the antihypertensive treatment in these patients which takes advantage from effects of these drugs beyond blood pressure reduction.

Renal immune cell infiltration and accompanying inflammation activates renal sodium transporters leading to sodium retention and hypertension. Lymphatic vessels traffic interstitial immune cells to the draining lymph nodes and help resolve inflammation. We have previously demonstrated that genetically inducing renal lymphangiogenesis prevents hypertension associated with a reduction in renal immune cell accumulation; however, it is unknown whether augmenting renal lymphatics can treat hypertension. Our hypothesis was that augmenting renal lymphatics after hypertension is established will lower blood pressure during L-NAME-induced hypertension (LHTN). Transgenic mice that overexpress the lymphangiogenic signal VEGF-D only in the kidney upon doxycycline administration (KidVD+ mice) and KidVD- littermates were administered L-NAME (0.5 mg/mL) in their drinking water for four weeks with doxycycline initiated at the second week of L-NAME. Treatment with L-NAME for one week induced LHTN in both KidVD- and KidVD+ mice (SBP: 134±4 and 142±5 mmHg, respectively). However, doxycycline-induced renal lymphangiogenesis significantly decreased blood pressure in KidVD+ mice compared to KidVD- mice after four weeks of L-NAME (SBP: 127±5 vs. 151±6 mmHg; p+ F4/80 - monocytes and a significant increase in 24-hour urinary sodium excretion and fractional excretion of sodium in KidVD+ mice. Urinary volume over 24 hours was also increased in KidVD+ mice (1.7±0.8 vs. 3±0.9 mL/24 hours; p

Primary hyperaldosteronism, or Conn’s syndrome, is a disorder of excessive secretion of aldosterone from the adrenal gland(s). The aldosterone excess results in sodium retention, volume expansion, and hypertension. Complications from long-standing disease include hypokalemia, arrhythmias, heart attack, and stroke.

Edema is a common complication of numerous renal disease. In the recent past several aspects of the pathophysiology of this condition have been elucidated. We herein present a case of nephrotic syndrome in a 30 year-old men. The discussion revolves around the following key questions on fluid accumulation in renal disease: 1. What is edema? What diseases can cause edema? 2. What are the mechanisms of edema in nephrotic syndrome? 2a. The “underfill” theory 2b. The “overfill” theory 2c. Tubulointerstitial inflammation 2d. Vascular permeability 3. What are the mechanisms of edema in nephritic syndrome? 4. How can the volume status be assessed in patients with nephrotic syndrome? 5. What are therapeutic strategies for edema management? 6. What are the factors affecting response to diuretics? 7. How can we overcome the diuretics resistance? 7a. Effective doses of loop diuretics 7b. Combined diuretic therapy 7c. Intravenous administration of diuretics 7d. Albumin infusions 7e. Alternative methods of edema management 8. Conclusion.

Patients with heart failure (HF) now rarely present in cardiogenic shock. Instead, HF has become a chronic systemic disease in which symptoms and disease progression are related to unrestrained neurohumoral stimulation, leading to water and sodium retention [(1)][1]. Because the kidneys are

Angiotensin-converting enzyme (ACE) plays a key role in renal inflammation and sodium retention associated with diabetic nephropathy. Although most effects of ACE have been classically related to angiotensin (Ang) II synthesis, studies highlight an Ang II-independent role of ACE in inflammation. Indeed, ACE has two catalytic domains, the N- and C-domains, that can process a wide diversity of substrates besides Ang I. Here, we study the relative contributions of ACE domains to renal inflammation and sodium retention during diabetic nephropathy. Diabetes was induced with streptozotocin in wild-type (WT) mice and mice lacking either a functional ACE N-domain (NKO) or C-domain (CKO) (n=5-8). After 6 months of diabetes, we evaluated the natriuretic response to volume expansion. For this, mice were injected with 0.9% NaCl equivalent to 10% of their body weight. After 5 hours, diabetic NKO mice excreted 30% more urinary sodium in response to the saline challenge compared to diabetic WT or CKO mice ( P P P P P P P =NS). We next evaluated whether the anti-inflammatory tetrapeptide N-acetyl-seryl-asparyl-lysyl-proline (AcSDKP), an ACE N-domain specific substrate, mediates the protective phenotype of NKO. For this, diabetic mice were treated with the prolyl oligopeptidase inhibitor, S17092 (10 mg/kg, IP), that prevents the synthesis of AcSDKP. In diabetic NKO mice receiving S17092, sodium excretion in response to a saline challenge, ENaC α and γ subunit cleavage, renal inflammation and renal injury were indistinguishable from equally treated diabetic WT mice. In summary, these data indicate that increasing AcSDKP by blocking the ACE N-domain improves sodium handling and ameliorates diabetic kidney disease independently of intrarenal Ang II regulation.

Aim: Hypertension (HTN) is positively correlated with age and sympathetic tone in humans. We hypothesize that sympathetically driven sodium chloride cotransporter (NCC)-mediated sodium retention contributes to age-related HTN. Methods: Three, 8 and 16 month old male SD rats on a normal salt (NS; 0.6% NaCl) diet underwent an acute IV volume expansion (VE; 5% body weight – mechanoreceptor stimulus) or 1M NaCl infusion (20μL/min, 2hr – chemoreceptor stimulus) and mean arterial pressure (MAP), natriuresis (UNaV) and paraventricular nucleus (PVN) neuronal activation (c-Fos expression) were assessed. In separate groups of rats fed a 21 day NS or high salt (HS; 4% NaCl) diet, 1) ex vivo afferent renal nerve (ARN) activity (norepinephrine-evoked substance P release) or 2) in vivo MAP, NCC activity (ΔUNaV to IV hydrochlorothiazide, 2mg/kg) and sympathetic tone were assessed. N=4-6/gp. Results: The natriuretic and PVN sympathoinhibitory parvocellular neuronal responses to VE, but not 1M NaCl infusion, are blunted in aged rats. Aged rats exhibit reduced ARN activity on a NS diet and fail to increase ARN activity on a HS diet. Aged rats develop salt sensitive HTN accompanied by elevated NCC activity and sympathetic tone on a NS diet and impaired suppression of NCC activity and sympathetic tone on a HS diet. Conclusion: Aging is associated with a selective impairment in the mechanosensitive ARN and salt sensitive HTN. We speculate that an age-related decrease in the mechanosensitive ARN sympathoinhibitory reno-renal reflex promotes sympathoexcitation, perhaps via reduced activity of PVN sympathoinhibitory parvocellular neurons, driving NCC-mediated sodium retention and salt sensitive HTN.

Creatine kinase (CK) rapidly regenerates ATP for Na(+)/K(+)‐ATPase driven sodium retention throughout the kidney. Therefore, we assessed whether resting plasma CK is associated with sodium retention after a high sodium diet. Sixty healthy men (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were assigned to low sodium intake ( 200 mmol/d). Sodium excretion (mmol/24‐h) after high sodium was 260.4 (28.3) in the high CK tertile versus 415.2 (26.3) mmol/24‐h in the low CK tertile (P

The renal nerves contribute to hypertension through effects in the kidney that enhance sodium retention and renin secretion, and by effects in the central nervous system that increase systemic sympathetic activity. Therefore, targeting the renal nerves provides a logical basis for treating hypertension. Several trials of renal denervation––achieved by applying radiofrequency energy through catheters placed in the renal arteries–– have been completed. Clinical results have been inconsistent, however, partly because of factors related to the ablation technique and partly because these studies have been performed in patients with the inadequately defined clinical condition of “treatment-resistant hypertension.” This statement now explains our conclusion that future studies of renal denervation should be guided by the established randomized, controlled clinical trial designs used for studying antihypertensive drugs and other treatments for hypertension. © 2015 Wiley Periodicals, Inc.

The renal nerves contribute to hypertension through effects in the kidney that enhance sodium retention and renin secretion, and by effects in the central nervous system that increase systemic sympathetic activity. Therefore, targeting the renal nerves provides a logical basis for treating hypertension. Several trials of renal denervation––achieved by applying radiofrequency energy through catheters placed in the renal arteries–– have been completed. Clinical results have been inconsistent, however, partly because of factors related to the ablation technique and partly because these studies have been performed in patients with the inadequately defined clinical condition of “treatment-resistant hypertension.” This statement now explains our conclusion that future studies of renal denervation should be guided by the established randomized, controlled clinical trial designs used for studying antihypertensive drugs and other treatments for hypertension. © 2015 Wiley Periodicals, Inc.

Congestion is the most important pathophysiological condition in the patients with hospitalization for heart failure (HHF). To manage congestion and improve outcome in the HHF patients, it is essential to understand historical process to reach the present concept of congestion and also its hemodynamic and neurohormonal mechanisms. Congestion consists of both sodium and water retentions. Sodium retention involves not only both renin-angiotensin-aldosterone system and sympathetic nerve system, but also vasopressin system. In contrast, water retention is mainly caused by activation of vasopressin system. Congestion caused by these mechanisms impairs the functions of multiorgans. The crosstalk between the heart and other organs is activated via both neurohormonal activation including vasopressin system and hemodynamic changes in HF. It causes the vicious cycle of congestion and finally it becomes life-threatening. Therefore, congestion including multi-organ congestions should be treated as early as possible with appropriate managements. The fundamental concept of treatment for the HHF patients based on clinical evidences, i.e., “the earlier, the better,” will be able to improve outcome for the HHF patients.

Hypertension (HTN) and high-salt diets are important risk factors for stroke and dementia. DOCA-salt is a recognized model of HTN driven by sodium retention and brain renin-angiotensin system (RAS) activation. However, it is unknown whether essential mechanisms regulating the cerebral circulation are altered in DOCA-salt mice, and, if so, whether these alterations are associated with cognitive impairment. To this end, C57BL/6 mice were implanted with 50mg DOCA pellets SQ and received 0.9% NaCl drinking water for 3 weeks. Cerebral blood flow (CBF) was measured in the somatosensory cortex by laser-Doppler flowmetry through a cranial window. DOCA-salt increased systolic blood pressure (BP; 148±3 vs 112±3 mmHg in controls; p0.05). PVM depletion improved novel object exploration (pgp91 mRNA in cerebral vessels from DOCA mice, which was prevented by PVM depletion (p

Background There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP).

Background: Urinary plasmin activates the epithelial Na + channel (ENaC) in vitro and may possibly be a mechanism of sodium retention in nephrotic syndrome (NS). This study used a paired design to test the hypothesis that remission of NS is associated with a decreased content of urinary plasmin and reduced ability of patients' urine to activate ENaC. Methods: Samples were collected during active NS and at stable remission from 20 patients with idiopathic NS, aged 9.1 ± 3.2 years. Plasminogen-plasmin concentration was measured with an enzyme-linked immunosorbent assay. Western immunoblotting for plasminogen-plasmin was performed in paired urine samples. The patch clamp technique was used to test the ability of urine to evoke an inward current on collecting duct cells and human lymphocytes. Results: The urinary plasminogen-plasmin/creatinine ratio was 226 [95 % confidence interval (CI) 130-503] μg/mmol in nephrotic urine versus 9.5 (95 % CI 8-12) μg/mmol at remission (p < 0.001). Western immunoblotting confirmed the presence of active plasmin in urine collected during active NS, while samples collected at remission were negative. Nephrotic urine generated an inward amiloride- and α 2-anti-plasmin- sensitive current, whereas the observed increase in current in urine collected at remission was significantly lower (201 ± 31 vs. 29 ± 10 %; p = 0.005). Conclusions: These findings support the hypothesis that aberrantly filtered plasminogen-plasmin may contribute to ENaC activation and mediate primary renal sodium retention during active childhood NS.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications purchased over the counter to treat acute and chronic pain and inflammation associated with a range of medical conditions.1 It is estimated that NSAIDs are prescribed to about 25% of Canadians for short-term use, but overall use is likely much higher with over-the-counter availability.2 Like any medication, the benefits of NSAIDs should be considered in tandem with the potential adverse effects. Side effects range from the mild and common to the severe and infrequent: dyspepsia, gastric or duodenal ulceration, sodium retention and subsequent hypertension, as well as increased incidence of cardiovascular (CV) adverse events. It was the withdrawal of rofecoxib from the market that brought to light the CV risk of NSAIDs and, in fact, a black-box warning now exists in NSAID product monographs, advising caution when prescribing to patients with ischemic heart disease, cerebrovascular disease and/or congestive heart failure.3 This article focuses on the CV effects associated with NSAID use by reviewing the recent literature on this topic.

Over 60 years ago, Dr. Irvine Page proposed the Mosaic Theory of hypertension, which states that many factors, including genetics, environment, adaptive, neural, mechanical and hormonal perturbations interdigitate to raise blood pressure. In the past two decades, it has become clear that common molecular and cellular events in various organs underlie many features of the Mosaic Theory. Two of these are the production of reactive oxygen species (ROS) and inflammation. These factors increase neuronal firing in specific brain centers, increase sympathetic outflow, alter vascular tone and morphology and promote sodium retention in the kidney. Moreover, factors such as genetics and environment contribute to oxidant generation and inflammation. Other common cellular signals, including calcium signaling and endoplasmic reticulum stress are similarly perturbed in different cells in hypertension and contribute to components of Dr. Page’s theory. Thus, Dr. Page’s Mosaic Theory formed a framework for future studies of molecular and cellular signals in the context of hypertension, and has greatly aided our understanding of this complex disease.

BACKGROUND: Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis.METHODS: Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured.RESULTS: The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p CONCLUSIONS: Losartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.

This chapter focuses on unintended drug-induced blood pressure responses. While both increases and decreases are legitimate areas of investigation (Kane-Gill et al. 2014; Kennelly and Esaian 2013), our attention falls on increases. As was noted in Sect. 3.4.4, high blood pressure is authoritative regarded as the greatest threat to the global burden of disease (Horton 2013; Das and Samarasekera 2013; Lim et al. 2013). As hypertension has been studied across several decades, we have learned that there are multiple ways in which increased blood pressure may occur (see Frohlich 1977; Page 1982; Dustan 1990; Harrison 2013). It has now also become clear that noncardiovascular drugs can lead to off-target increases in blood pressure and can also do so via a variety of mechanisms of action. As Grossman and Messerli (2012) observed, “Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower BP may paradoxically increase BP, or an increase in pressure may be encountered after their discontinuation.”

This study aims at assessing the modifications of renal parameters with 13 female players of the same Benin team-amateur Division 1, during two consecutive handball games played 26 hours apart. The players are divided into two groups: starters (ST: N = 7) and nonstarters (NS: N = 6). The estimated glomerular filtration rate (eGFR) with Cockcroft-Gault and MDRD formulae, the fractional excretion of sodium (FeNa), the plasma haemoglobin (Hb) and albumin (Alb) were assayed at rest and at the end of each game. At the end of the first game, only eGFR decreased significantly by at least 16.30% (p 0.05). FeNa varied in no group, neither after the first game, nor after the second (p > 0.05). But a cumulative reduction is observed between the values before the first and those recorded at the end of the second game in both ST and NS groups. The status of the players (ST or NS) did not influence the results. Two games of handball played 26 hours apart in the sub-Saharan environment of Cotonou caused in girls, a transitory decrease in eGFR without a cumulative effect. FeNa decreased too, but with a cumulative effect which indicates large sodium retention.

A cross-sectional study was conducted in 156 clinically-stable peritoneal dialysis patients to identify the factors associated with sodium removal. Serum biochemistry, peritoneal function (modified peritoneal equilibration test [PET]) and the adequacy of dialysis were analysed in relation to sodium removal using multivariate linear regression. Factors significantly affecting peritoneal sodium removal included infusion volume and ultrafiltration volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. Factors significantly affecting total sodium removal included ultrafiltration and urine volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. With traditional dialysate, adequate fluid removal is required to ensure sufficient sodium removal, but a low-sodium dialysate may prevent sodium retention. Sodium removal should be included in evaluation of the adequacy of dialysis.

Insulin-mediated sodium retention is implicated as a mechanism for hypertension in metabolic syndrome and type II diabetes. However, there is no direct experimental evidence for a sustained antinatriuretic effect of insulin outside of rodents, and all previous studies in dogs have been negative. This study used a novel approach to test for a chronic sodium-retaining action of insulin in dogs, by testing the hypothesis that natriuresis in type I diabetes is dependent on the decrease in insulin, rather than being due solely to osmotic actions of hyperglycemia. Dogs were chronically instrumented and housed in metabolic cages. Fasting blood glucose in alloxan-treated dogs was maintained at ∼65 mg/dl by continuous intravenous insulin infusion. Then, a 6-day diabetic period was induced by either 1) decreasing the insulin infusion to induce type I diabetes (D; blood glucose = 449 ± 40 mg/dl) or 2) clamping the insulin infusion and infusing glucose continuously (DG; blood glucose = 470 ± 56 mg/dl). Control urinary sodium excretion (UnaV) averaged 70 ± 5 (D) and 69 ± 5 (DG) meq/day and increased on day 1 in both groups. UnaV remained elevated in the D group (115 ± 15 meq/day days 2– 6), but it returned to control in the DG group (69 ± 11 meq/day days 2– 6) and was accompanied by decreased lithium clearance. Thus, insulin had a sustained antinatriuretic action that was triggered by increased glucose, and it was powerful enough to completely block the natriuresis caused by hyperglycemia. These data may reveal an unrecognized physiologic function of insulin as a protector against hyperglycemia-induced salt wasting in diabetes.

The nephrotic syndrome is defined by a urinary protein excretion exceeding 3g per day, associated with hypoalbuminaemia (< 30 g/L) and hypoprotidaemia (< 60 g/L). The clinical consequences of the nephrotic syndrome are multiple, essentially dominated by sodium retention and oedema formation. The oedema physiopathology is related to both increased capillary permeability and primary activation of the Na/K pump in the collect duct. Other complications of the nephrotic syndrome include thromboembolic complications, dyslipidaemia, and infections. The treatment of these complications represents an important part of the general management of the nephritic syndrome.

Heart failure constitutes a significant source of morbidity and mortality in the United Sta-tes and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associatedwith adverse clinical outcomes. This interaction, termed the cardiorenal syndrome, is a complex phe-nomenon characterized by a pathophysiological dise-quilibrium between the heart and the kidney, in which malfunction of one organ subsequently promotes the impairment of the other.Multiple neuro-humoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic pepti-des, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs in order to secure better clinical outcomes. To this end, a multidisciplinary ap-proach is recommended to achieve optimal results.

Hyponatremia is one of the newer and emerging risk factors for an adverse prognosis in chronic heart failure. Why decreased serum sodium is associated with worse prognosis remains unclear. It may reflect worsening heart failure and the deleterious effects of activation of neurohormones. The mechanism of hyponatremia in heart failure also remains unclear. A relatively greater degree of free-water retention compared to sodium retention is probably the major mechanism. The treatment of significant hyponatremia in heart failure is difficult. The conventional treatments such as fluid restriction, infusion of hypertonic saline, and aggressive diuretic therapies are not usually effective. Vasopressin receptor antagonists have been shown to enhance aquaresis and correct hyponatremia. However, long-term beneficial effects of such treatments in chronic heart failure have not been documented.

Licorice, a plant indigenous to southern Europe, the Middle East, and northern China, exhibits several pharmacological properties, including estrogenic, anti-tumoral, anti-inflammatory, anti-allergenic, and anti-tussive activities. Prolonged use of licorice is known to produce headaches, hypertension, cardiac arrhythmias, edema, lethargy, dyspnea, sodium retention and loss of potassium in humans. However, to date, the potential adverse health effects due to occupational inhalation exposure of licorice root dust remains unknown. This study was, therefore, undertaken to address this issue. In this cross-sectional study, individuals (30 workers) occupationally exposed to licorice root dust at a licorice producing plant in Shiraz, Iran were recruited. Similarly, 30 healthy male unexposed employees at a telecommunications industry, with identical demographic and socioeconomic status, without any past or current exposure to licorice dust or habitual ingestion of this compound, served as the referent group. Syst...

The renal nerves contribute to hypertension through effects in the kidney that enhance sodium retention and renin secretion, and by effects in the central nervous system that increase systemic sympathetic activity. Therefore, targeting the renal nerves provides a logical basis for treating hypertension. Several trials of renal denervation––achieved by applying radiofrequency energy through catheters placed in the renal arteries–– have been completed. Clinical results have been inconsistent, however, partly because of factors related to the ablation technique and partly because these studies have been performed in patients with the inadequately defined clinical condition of “treatment-resistant hypertension.” This statement now explains our conclusion that future studies of renal denervation should be guided by the established randomized, controlled clinical trial designs used for studying antihypertensive drugs and other treatments for hypertension. © 2015 Wiley Periodicals, Inc.

Urine extracts as well as plasma and urine fractions from normal persons during extracellular volume expansion and from patients with edema of different origin were tested for natriuretic (rat bioassay) and antinatriferetic (frog skin) activity. Whereas the extracts and fractions from normal persons with extracellular volume expansion proved to have a distinct natriuretic and antinatriferetic effect, no such effect was observed with urine and plasma preparations from patients with sodium retention and edema. Whether or not edema formation is mediated by a loss of natriuretic activity remains still to be clarified.

After myocardial infarction (MI), cardiac remodeling activates Renin-Angiotensin-Aldosterone system (RAAS), which causes sodium (Na+)-induced plasma expansion, a contributor to ventricular dilation...

Die Regulation des arteriellen Blutdrucks ist ein komplexer Prozess. Dabei spielt die Niere eine wichtige Rolle, und sie ist bei der Entstehung und Fortdauer eines essentiellen Bluthochdrucks beteiligt. Mehrere Mechanismen spielen dabei eine Rolle: 1. das sympathische Nervensystem, 2. das Renin-Angiotensin-System, 3. die Regelung des Natrium- und Wasserhaushalts, 4. die Freisetzung vasoaktiver Substanzen wie z. B. Endothelin, Adenosin oder Stickstoff-Monoxid (NO) und 5. strukturelle Anderungen wie eine verringerte Anzahl von Glomeruli und Nephronen. Einige therapeutische Strategien, die diese Mechanismen beeinflussen, haben sich bereits als wirkungsvolle Bluthochdruckmittel erwiesen.

During the course of evolution, life forms moved from an aquatic to a terrestrial environment and a need for salt conservation arose. The neurohormonal defense systems that evolved to ensure salt and circulatory homeostasis have been essential for survival. For instance, the renin–angiotensin–aldosterone system (RAAS) played a fundamental role in promoting water and sodium retention, and in facilitating potassium excretion in prehistoric humans, hunter-gatherers who consumed a diet high in potassium and who were prone to death from hemorrhage or diarrhea [1]. As our living conditions have changed over millions of years, however, the need for salt conservation has diminished and the neurohormonal systems essential to survival in prehistoric times may become maladaptive under select circumstances. Consequently, the term neurohormonal activation often has a negative connotation, despite it being a mechanism essential for species preservation under some conditions. This article focuses on the adverse effects of neurohormonal activation, acknowledging that it is

Increased sodium (Na(+)) retention in blacks could be related to the high prevalence of hypertension in adult blacks. Na(+) retention in response to controlled dietary Na(+) has not been rigorously compared in the different race groups. The present study assessed Na(+) retention in 22 black and 14 white girls, 11-15 yr old, during 3 wk on a low (1.3 g, 57 mmol)- and during 3 wk on a high (4 g, 172 mmol)-Na(+) diet in a randomized order, crossover design. Subjects were matched by postmenarcheal age and weight. After a 1-wk equilibration period, the mean daily Na(+) retention was 357 +/- 69 mg (15.5 +/- 3.0 mmol) in blacks and 239 +/- 37 mg (10.4 +/- 1.6 mmol) in whites on the low-Na(+) diet and 991 +/- 138 mg (43.1 +/- 6.0 mmol) in blacks vs. 334 +/- 90 mg (14.5 +/- 3.9 mmol) in whites (P < 0.001) on the high-Na(+) diet. The greater Na(+) retention in blacks was not accompanied by an increase in fecal or sweat Na(+) excretion. Blood pressure and weight did not increase despite the Na(+) retention, and thus, the retained Na(+) appeared to reside in a nonextracellular compartment that we speculate to be bone. In summary, black girls showed greater Na(+) retention compared with white girls. The difference in Na(+) handling may contribute to underlying racial differences in susceptibility to hypertension.

Background/Aims: The role of COX-2 for renal function during renal development, for physiology and pathophysiology of renal diseases and the side effects of available COX-2 inhibitors, has gained increasing interest. We aimed therefore to review the respective role of renal COX-2. Methods: Review of relevant recent publications in the field, and in addition of in part unpublished data obtained in our laboratories. Results: COX-2 is ‘constitutively’ localized in the kidney i.e. in macula densa, TALH, interstitial cells, and is of utmost importance for normal renal development. Renal COX-2 is regulated by for example sodium and volume intake, angiotensin II, glucocorticoids often involving specific COX-2 promotor response elements. COX-2 derived prostanoids are required for preservation of renal blood flow and glomerular filtration especially in states of fluid deficit, they promote natriuresis, and furthermore may stimulate renin secretion during low-sodium intake/loop diuretic use. Conversely, COX-2 inhibitors decrease glomerular filtration, and renal perfusion, sometimes even causing acute renal failure. In addition, COX-2 inhibitors cause sodium retention, edema formation, cardiac failure and hypertension. The role of COX-2 derived prostanoids in renal inflammation or failure including diabetic nephropathy and renal transplantation remains at present controversial. Conclusion: COX-2 is one of the major players in renal physiology and pathophysiology. One focus of future work should be placed on COX-2 in primary renal diseases.

Kidney and hypertension. There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that “blood pressure goes with the kidney,” a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.

Summary Preeclampsia and eclampsia have a relationship with perinatal morbimortality, and intrauterine growth retardation, because there is generalised angiospasm with water and sodium retention and alterations in uterine contractility which have repercussions on maternalfoetal binomial. From this came the interest in determining FHR variations originated by uterine contractility induced with oxytocin, to see if a correlation exists between accelerations and type II dips, and to compare the results obtained with a sample of anaemic pregnant women. In both groups the common denominator is chronic foetal hypoxia. The hypothesis was, that there is a correlation between accelerations of great frequency and amplitude (probably of hypoxic origin), and Type II dips. There were 12 patients in the sample, with a diagnosis of mild preeclampsia. Their mean age had a standard variation of 25.9; 7.00 years, and pregnancy age had a mean and standard deviation of 36.00; 2.13 weeks. The uterine contractility and Foetal Heart Rate (FHR) register were made using a Hewlett Packard monitor, Model 1350 of the 50MX series. During the first 90 minutes uterine contractility and FHR were recorded in the control group (basal values), to compare them with those obtained under the effect of oxytocin (uterine contraction tolerance test) in the problem group. The values of the basal FHR were in a range of 108-155 beats/min, with a mean and standard deviation from 136.09; 8.12 beats/min. The values were confronted with the sample of anaemic patients: in a range from 112-158 beats/min; with a mean and standard deviation from 142.81; 10.70 beats/min. The difference between means was significant, with a 0.05 Alpha. Statistical analysis revealed that the frequency of accelerations was greater in the group of patients with anaemia, following oxytocin. The frequency of Type II dips was greater in anaemic patients who did not have oxytocin. The frequency of Type II dips in the group of preeclamptic patients with oxytocin was greater; in the three confrontations the differences were significant. Newborns of toxaemic mothers had poor oxygen reserves. Caesarean section improve the both the physical state of newborns and their prognosis.

This review emphasizes that whatever the pathogenesis of pre-eclampsia, the ultimate target is the maternal vascular endothelium which is in abundance within the kidneys. Glomerular capillary endotheliosis is accompanied by decreased renal haemodynamics, disordered renal vascular sensitivity, hypofiltration and loss of permselectivity with non-selective proteinura. Altered tubular function contributes to sodium retention and hypercuricaemia. Occasionally, functional impairment is very severe with both tubular and cortical necrosis. The renal changes of pre-eclampsia are usually fully reversible.

The nephrotic syndrome is defined by a urinary protein level exceeding 3.5 g per 1.73 m2 of body-surface area per day. At the turn of the century, clinicians distinguished a nephritic syndrome of inflammatory origin and a nephrotic syndrome of presumed degenerative origin. Today these concepts are outmoded, but the term “nephrotic syndrome” is clinically useful and has persisted, because heavy proteinuria, irrespective of its origin, is associated with a spectrum of clinically important sequelae, particularly sodium retention, hyperlipoproteinemia, and thromboembolic and infectious complications. The definition given above is arbitrary, however, and special significance should not be given to the . . .

Total parenteral nutrition may induce harmful water and sodium retention. Few efforts have been made to elucidate the mechanisms of this deleterious response to total parenteral nutrition. In this review we discuss the different factors involved in its pathophysiology and possible changes in total parenteral nutrition regimes in order to modulate such a response: reduction of the proportion of non-protein calories given as glucose, restriction of water and sodium, and the possible benefits of pharmaceutical nutritional therapy with glutamine and growth hormone.

GH treatment of adult patients with GH deficiency (GHD) or healthy volunteers results in weight gain and fluid and sodium retention. In the present study we have challenged normal short children with dehydration and water load, and evaluated their water and sodium clearance, plasma renin activity (PRA) and aldosterone over 4 weeks of GH administration. Eleven prepubertal short normal children, aged 4–9 years, were the subjects of this study. Recombinant GH was administered daily at a dose of 2.5 units/m2. Dehydration and water load experiments were conducted before GH (day 0) and on days 3, 7 or 28 of GH. An initial 15-hour fast ended with a 3-hour urine collection. A tap-water load of 800 ml/m2 was given orally. Urinary volumes were followed hourly for 3 h, as were urinary and serum creatinine, Na, K, aldosterone, plasma osmolality and PRA. Before GH therapy the subjects excreted within 2 h a mean 42% and within 3 h a mean 65% of the load. After 3 days of GH therapy the same children retained water significantly and excreted only 22 (p < 0.02) and 45% (p < 0.05) of the load volume, respectively. Calculating the free water clearance revealed no effect of GH therapy, whereas the fractional excretion of sodium and potassium decreased significantly by day 3 of GH administration, along with an increase in PRA and serum aldosterone. All these changes normalized by days 7 and 28 of GH therapy. It is concluded that short-term administration of GH to short normal children results in a transitory mild retention of sodium and a secondary water retention, and suggests that the primary event leading to sodium retention during the early phase of GH therapy of short normal children is an inappropriate increase in PRA.