scholarly journals Is Renal β-Adrenergic-WNK4-NCC Pathway Important in Salt Hypertension of Dahl Rats?

2019 ◽  
pp. 873-882 ◽  
Author(s):  
J. Zicha ◽  
S. Hojná ◽  
Z. Vaňourková ◽  
L. Kopkan ◽  
I. Vaněčková
Keyword(s):  
Sodium Excretion ◽  
Salt Intake ◽  
Adrenergic Stimulation ◽  
Salt Diet ◽  
Low Salt ◽  
Salt Hypertension ◽  
Propranolol Treatment ◽  
Β Blocker ◽  
Hypertension Development ◽  
Experimental Group

In 2011 Fujita and coworkers proposed that β-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents. The aim of our study was to investigate whether the above hypothesis is also valid for salt hypertension of Dahl rats, which are characterized by high sympathetic tone and abnormal renal sodium handling. Male 8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats were fed either low-salt diet (LS, 0.4 % NaCl) or high-salt diet (HS, 4 % NaCl) for 6 weeks. Half of the animals on either diet were chronically treated with non-selective β-blocker propranolol (100 mg/kg/day). At the end of the experiment diuresis and sodium excretion were measured prior and after hydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.). Furthermore, blood pressure (BP), heart rate (HR), sympathetic (pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kg i.v.) BP components were determined. Chronic HS diet feeding increased BP through sympathoexcitation in SS/Jr but not in SR/Jr rats. Concomitant propranolol treatment did not lower BP in either experimental group. Under the conditions of low salt intake HCTZ increased diuresis, natriuresis and fractional sodium excretion in SR/Jr but not in SS/Jr rats. HS diet feeding attenuated renal response to HCT in SR/Jr rats, whereas no HCTZ effect was observed in SS/Jr rats fed HS diet. Propranolol treatment did not modify diuresis or natriuresis in any experimental group. In conclusions, our present data do not support the idea on the essential importance of renal β-adrenergic-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats.

scholarly journals Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase

2012 ◽  
Vol 13 (3) ◽  
pp. 353-359 ◽  
Author(s):  
MA Bayorh ◽  
A Rollins-Hairston ◽  
J Adiyiah ◽  
D Lyn ◽  
D Eatman
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Prostaglandin E ◽  
Renal Tubules ◽  
Protective Effects ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Low Salt ◽  
Cox 2

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E2 (PGE2). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE2. The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.

scholarly journals ‘Low-Salt’ Bread as an Important Component of a Pragmatic Reduced-Salt Diet for Lowering Blood Pressure in Adults with Elevated Blood Pressure

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1725 ◽  
Author(s):  
Kevin D. Cashman ◽  
Sorcha Kenny ◽  
Joseph P. Kerry ◽  
Fanny Leenhardt ◽  
Elke K. Arendt
Keyword(s):  
Blood Pressure ◽  
Bone Metabolism ◽  
Plasma Lipids ◽  
Salt Intake ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Salt Diet ◽  
Low Salt ◽  
Dietary Period ◽  
Reduced Salt

Reformulation of bread in terms of salt content remains an important measure to help achieve a reduction in salt intake in the population and for the prevention of hypertension and elevated blood pressure (BP). Our fundamental studies on the reduction of salt on dough and bread characteristics showed that wheat breads produced with 0.3 g salt/100 g (“low-salt”) were found to be comparable quality to that produced with the typical level of salt (1.2%). This food-based intervention trial examined, using a 5 week cross-over design, the potential for inclusion of “low-salt” bread as part of a pragmatic reduced-salt diet on BP, markers of bone metabolism, and plasma lipids in 97 adults with slightly to moderately elevated BP. Assuming all sodium from dietary intake was excreted through the urine, the intake of salt decreased by 1.7 g/day, on average, during the reduced-salt dietary period. Systolic BP was significantly lower (by 3.3 mmHg on average; p < 0.0001) during the reduced-salt dietary period compared to the usual-salt dietary period, but there was no significant difference (p = 0.81) in diastolic BP. There were no significant differences (p > 0.12, in all cases) in any of the urinary- or serum-based biochemical indices of calcium or bone metabolism or in plasma lipids between the two periods. In conclusion, a modest reduction in dietary salt intake, in which the use of “low-salt” (i.e., 0.3 g/100g) bread played a key role along with dietary advice, and led to a significant, and clinically meaningful, decrease in systolic, but not diastolic, BP in adults with mildly to moderately elevated BP.

Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. R410-R417 ◽  
Author(s):  
Atsushi Sakima ◽  
Hiroshi Teruya ◽  
Masanobu Yamazato ◽  
Rijiko Matayoshi ◽  
Hiromi Muratani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
High Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
Air Jet ◽  
Sd Rats ◽  
Low Salt ◽  
The Brain

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg ⋅ kg−1 ⋅ day−1of N G-monomethyl-l-arginine (l-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 ± 3 mmHg vs. 114 ± 3, 113 ± 1, and 108 ± 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats givenl-NMMA than in rats given aCSF (29 ± 4% vs. 19 ± 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats givenl-NMMA than in rats given aCSF irrespective of salt intake, although the difference was ∼7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.

Postprandial natriuresis in humans: further evidence that urodilatin, not ANP, modulates sodium excretion

1996 ◽  
Vol 270 (2) ◽  
pp. F301-F310 ◽  
Author(s):  
C. Drummer ◽  
W. Franck ◽  
M. Heer ◽  
W. G. Forssmann ◽  
R. Gerzer ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Sodium Excretion ◽  
Salt Intake ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
High Salt ◽  
Peak Rate ◽  
High Salt Intake ◽  
Low Salt ◽  
Chloride Excretion

We examined the effects of a high-salt (100 mmol NaCl) and a low-salt (5 mmol NaCl) meal on the renal excretion of sodium and chloride in 12 healthy male upright subjects. We also measured the urinary excretion of urodilatin [ANP-(95-126)], and the plasma or serum concentrations of atrial natriuretic peptide [ANP-(99-126)], aldosterone, and renin. The high-salt meal produced a postprandial natriuresis (urinary sodium excretion from 59.0 to a peak rate of 204.6 mumol/min in 3rd h after ingestion of meal) and chloride excretion. In parallel, the urinary excretion of urodilatin increased from 35.7 to a peak rate of 105 fmol/min. The effect of high-salt intake on urinary sodium, chloride, and urodilatin excretion was significant (analysis of variance, P < 0.01), and close significant correlations were observed between urodilatin and sodium excretion (mean R = 0.702) as well as between urodilatin and chloride excretion (mean R = 0.776). In contrast, plasma ANP, which was acutely elevated 15 min after high-salt intake, was already back to low-salt values 1 h later. It did not parallel the postprandial natriuretic profile, and no positive correlation between plasma ANP and sodium excretion was observed. These results provide further evidence that urodilatin, not ANP, is the member of this peptide family primarily involved in the regulation of the excretion of sodium and chloride.

Salt intake and insulin sensitivity in healthy human volunteers

2007 ◽  
Vol 113 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Raymond R. Townsend ◽  
Shiv Kapoor ◽  
Christopher B. McFadden
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Infusion ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Euglycaemic Clamp ◽  
Noradrenaline Concentration ◽  
Low Salt

The literature on salt intake and insulin sensitivity presents a mixed picture, as some studies have shown an increase, whereas others have shown a decrease, in insulin action as sodium intake is enhanced. In some cases, this may relate to the study of salt intake in patients with co-morbidities such as hypertension or diabetes. In the present study, we selected healthy normotensive lean volunteers who underwent a euglycaemic clamp following 6 days of a low-salt diet (20 mmol sodium daily) and, subsequently, 6 days of a high-salt diet (200 mmol sodium daily). Our results show an increase in insulin-mediated glucose disposal during euglycaemic clamp conditions that was significantly higher following the high-salt diet compared with the low-salt diet (7.41±0.41 compared with 6.11±0.40 mg·kg−1 of body weight·min−1 respectively; P=0.03). We measured calf blood flow before and during insulin infusion (no significant change after the two dietary salt interventions was detected) and plasma non-esterified fatty acids (also no significant differences were detected). We observed the expected increases in renin concentration and aldosterone activity in subjects on the low-salt diet, and also observed a significantly less increase in plasma noradrenaline concentration during euglycaemic insulin infusion following the high-salt compared with the low-salt diet. We propose that the 4–5-fold increase in serum aldosterone and the greater increase in plasma noradrenaline concentration following the low-salt intervention compared with the high-salt period may have contributed to the differences in insulin sensitivity following the adjustment in dietary sodium intake.

Propranolol induces acute natriuresis by β blockade and dopaminergic stimulation

1976 ◽  
Vol 54 (5) ◽  
pp. 683-691 ◽  
Author(s):  
M. C. Carrara ◽  
A. D. Baines
Keyword(s):  
Heart Rate ◽  
Sodium Excretion ◽  
Fold Increase ◽  
Nerve Function ◽  
Distal Nephron ◽  
Salt Diet ◽  
Blocking Effects ◽  
Low Salt ◽  
Dopaminergic Stimulation ◽  
Postganglionic Nerve

dl-Propranolol (0.8–1.6 mg/kg∙h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin–angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by β blockade and requires postganglionic nerve function but is independent of α receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal β blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking β receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

Cardiology ◽  
2015 ◽  
Vol 130 (4) ◽  
pp. 242-248 ◽  
Author(s):  
Yang Wang ◽  
Dan Wang ◽  
Chao Chu ◽  
Jian-Jun Mu ◽  
Man Wang ◽  
...  
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Potassium ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Potassium Intake ◽  
Potassium Supplementation ◽  
Low Salt

Objective: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Methods: Forty-two subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Results: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. Conclusions: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.

scholarly journals Modulation of Plasma Sphingosine-1-phosphate Levels via Dietary Salt Intervention in Chinese Adults: An Intervention Trial

2020 ◽  
Author(s):  
Qiong Ma ◽  
Chao Chu ◽  
Yanbo Xue ◽  
Yu Yan ◽  
Jiawen Hu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Repeated Measures ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
Chinese Adults ◽  
Salt Diet ◽  
Low Salt ◽  
Sphingosine 1 Phosphate ◽  
Pressure Modulation

Abstract Background: Salt is a crucial factor for blood pressure modulation, especially in salt-sensitive individuals. Sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite participating in blood pressure regulation, has recently been identified as a novel lipid diuretic factor. However, the relationships among salt intake, circulating S1P levels, and blood pressure changes in human beings are unknown. Thus, we conducted this intervention trial to explore the effect of dietary salt intake on plasma S1P levels and to examine the relationship between S1P and blood pressure in Chinese adults.Methods: 42 participants (aged 18–65 years) were recruited from a rural community in Shaanxi, China. All participants first maintained their normal diet for 3 days, then sequentially ate a low-sodium diet (3.0 g/day NaCl) for 7 days, followed by a high-sodium diet (18.0 g/day NaCl) for 7 days. We assessed their plasma S1P concentrations on the last day of each intervention phase by liquid chromatography-tandem mass spectrometry. We classified the subjects who demonstrated at least a 10% increase in mean arterial pressure upon transitioning from a low-salt to a high-salt diet as salt-sensitive and the others as salt-resistant. Differences in repeated measures were analyzed by repeated-measures analysis of variance. Results: Plasma S1P levels decreased significantly from the baseline to low-salt diet period and increased from the low-salt to high-salt diet period. We observed this response in both salt-sensitive and salt-resistant individuals. Plasma S1P levels positively correlated with 24-hour urinary sodium excretion, but not 24-hour urinary potassium excretion. In line with plasma S1P level responses to salt intervention, systolic blood pressure (SBP) and mean arterial pressure (MAP) decreased from the baseline to low-salt diet period and increased from the low-salt to high-salt period. SBP positively correlated with plasma S1P and the correlation was stronger in salt-sensitive individuals than that in salt-resistant individuals. Conclusion: Low-salt dietary intervention decreases plasma S1P levels, whereas high-salt intervention reverses this change and S1P levels positively correlated with SBP in Chinese adults. This provides a high-efficiency and low-cost intervention for plasma S1P levels modulation, with implications for salt-induced blood pressure modulation. Trial registration: NCT02915315. Registered 27 September 2016, http://www.clinicaltrials.gov

scholarly journals Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney

2013 ◽  
Vol 305 (12) ◽  
pp. F1680-F1686 ◽  
Author(s):  
Ming-Zhi Zhang ◽  
Yinqiu Wang ◽  
Bing Yao ◽  
Leslie Gewin ◽  
Shouzuo Wei ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Urine Volume ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
High Salt ◽  
Epoxyeicosatrienoic Acids ◽  
Wild Type ◽  
Salt Diet ◽  
Low Salt ◽  
Renal Dopamine

We have recently demonstrated that intrarenal dopamine plays an important role in preventing the development of systemic hypertension. Similarly, renal cytochrome P-450 (CYP)-epoxygenase-derived arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), also are antihypertensive through inhibiting sodium reabsorption and vasodilation. The potential interaction between renal dopamine and epoxygenase systems was investigated. Catechol- O-methyl-transferase (COMT)−/− mice with increased intrarenal dopamine levels and proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC−/−) mice with renal dopamine deficiency were treated with a low-salt diet or high-salt diet for 2 wk. Wild-type or Cyp2c44−/− mice were treated with gludopa, which selectively increased renal dopamine levels. In low salt-treated mice, urinary EET levels were related to renal dopamine levels, being highest in COMT−/− mice and lowest in ptAADC−/− mice. In high salt-treated mice, total EET and individual EET levels in both the kidney and urine were also highest in COMT−/− mice and lowest in ptAADC−/− mice. Selective increases in renal dopamine in response to gludopa administration led to marked increases in both total and all individual EET levels in the kidney without any changes in blood levels. qRT-PCR and immunoblotting indicated that gludopa increased renal Cyp2c44 mRNA and protein levels. Gludopa induced marked increases in urine volume and urinary sodium excretion in wild-type mice. In contrast, gludopa did not induce significant increases in urine volume or urinary sodium excretion in Cyp2c44−/− mice. These studies demonstrate that renal EET levels are maintained by intrarenal dopamine, and Cyp2c44-derived EETs play an important role in intrarenal dopamine-induced natriuresis and diuresis.

Regulation ofP-450 4A activity in the glomerulus of the rat

1999 ◽  
Vol 276 (6) ◽  
pp. R1749-R1757 ◽  
Author(s):  
Osamu Ito ◽  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Salt Intake ◽  
High Salt ◽  
Dependent Manner ◽  
Hydroxyeicosatetraenoic Acid ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Low Salt

We recently reported that an enzyme of the cytochrome P-450 4A family is expressed in the glomerulus, but there is no evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) can be produced by this tissue. The purpose of present study was to determine whether glomeruli isolated from the kidney of rats can produce 20-HETE and whether the production of this metabolite is regulated by nitric oxide (NO) and dietary salt intake. Isolated glomeruli produced 20-HETE, dihydroxyeicosatrienoic acids, and 12-hydroxyeicosatetraenoic acid (4.13 ± 0.38, 4.20 ± 0.38, and 2.10 ± 0.20 pmol ⋅ min−1⋅ mg protein−1, respectively) when incubated with arachidonic acid (10 μM). The formation of 20-HETE was dependent on the availability of NADPH and the[Formula: see text] of the incubation medium. The formation of 20-HETE was inhibited by NO donors in a concentration-dependent manner. The production of 20-HETE was greater in glomeruli isolated from the kidneys of rats fed a low-salt diet than in kidneys of rats fed a high-salt diet (5.67 ± 0.32 vs. 2.83 ± 0.32 pmol ⋅ min−1⋅ mg protein−1). Immunoblot experiments indicated that the expression of P-450 4A protein in glomeruli from the kidneys of rats fed a low-salt diet was sixfold higher than in kidneys of rats fed a high-salt diet. These results indicate that arachidonic acid is primarily metabolized to 20-HETE and dihydroxyeicosatrienoic acids in glomeruli and that glomerular P-450 activity is modulated by NO and dietary salt intake.

Sign in / Sign up

Export Citation Format

Share Document