Salt loading enhances rat renal TxA2/PGH2 receptor expression and TGF response to U-46,619

1997 ◽  
Vol 273 (6) ◽  
pp. F976-F983 ◽  
Author(s):  
William J. Welch ◽  
Bo Peng ◽  
Kazuhisa Takeuchi ◽  
Keishi Abe ◽  
Christopher S. Wilcox
Keyword(s):  
Salt Intake ◽  
Receptor Activation ◽  
High Salt ◽  
Receptor Expression ◽  
Tubuloglomerular Feedback ◽  
Kidney Cortex ◽  
Salt Loading ◽  
Receptor Mrna ◽  
High Salt Intake ◽  
Low Salt

The tubuloglomerular feedback (TGF) response is potentiated by thromboxane A2(TxA2) and/or prostaglandin endoperoxide (PGH2) acting on specific receptors. Infusion of the TxA2/PGH2mimetic, U-46,619, into conscious rats leads to hypertension that is potentiated by a high-salt intake. Therefore, we tested the hypothesis that a high-salt intake enhances the expression of transcripts for TxA2/PGH2receptors in the kidney and glomeruli and enhances the response of TGF to TxA2/PGH2receptor stimulation. Groups of rats were accommodated to a low-salt (LS), normal salt (NS), or high-salt (HS) diet for 8–10 days. TxA2/PGH2receptor mRNA was detected by reverse transcription-polymerase chain reaction in kidney cortex, isolated glomeruli, and abdominal aorta. TxA2/PGH2mRNA abundance was significantly ( P< 0.001) increased during intake of high-salt compared with low-salt diets in the kidney cortex (1.34 ± 0.10 vs. 0.84 ± 0.04 arbitrary units) and isolated outer cortical glomeruli (0.68 ± 0.04 vs. 0.32 ± 0.03 arbitrary units), but there was no effect of salt on TxA2/PGH2receptor mRNA expression in the aorta. Maximal TGF responses were assessed from the increase in proximal stop flow pressure (an index of glomerular capillary pressure) during increases in loop of Henle perfusion with artificial tubular fluid from 0 to 40 nl/min. Compared with vehicle, the enhancement of maximal TGF with U-46,619 (10−6 M) added to the perfusate was greater in rats adapted to high-salt than normal salt (HS: +9.6 ± 1.1 vs. NS: +5.1 ± 0.4 mmHg; P < 0.001) or low-salt (LS: +3.8 ± 1.3 mmHg; P < 0.001) intakes. Responses to U-46,619 at each level of salt intake were blocked by >70% by the TxA2/PGH2receptor antagonist ifetroban. In contrast, enhancement of TGF by peritubular capillary perfusion of arginine vasopressin (AVP; 10−7 M) was similar in high-salt and low-salt rats (HS: +1.5 ± 0.6 vs. LS: +1.6 ± 0.5 mmHg; not significant). We conclude that salt loading increases selectively the abundance of TxA2/PGH2receptor transcripts in the kidney cortex and glomerulus, relative to the aorta, and enhances selectively TGF responses to TxA2/PGH2receptor activation but not to AVP.

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.

Factors affecting Potassium Balance During Frusemide Administration

1984 ◽  
Vol 67 (2) ◽  
pp. 195-203 ◽  
Author(s):  
Christopher S. Wilcox ◽  
William E. Mitch ◽  
Ralph A. Kelly ◽  
Paul A. Friedman ◽  
Paul F. Souney ◽  
...  
Keyword(s):  
Salt Intake ◽  
Normal Subjects ◽  
Plasma Aldosterone ◽  
High Salt ◽  
Renin Angiotensin Aldosterone System ◽  
Plasma Aldosterone Concentration ◽  
Water Load ◽  
Renin Angiotensin ◽  
High Salt Intake ◽  
Low Salt

1. We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and antidiuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given. 2. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral. 3. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (−86 ± 7 mmol/3 days; P < 0.001). 4. Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance. 5. When a water load was given concurrently with frusemide, the acute kaliuresis was >30% lower compared with that seen with frusemide alone, even though the natriuretic response was unchanged. 6. We conclude that: (a) K+ balance is maintained when frusemide is given during liberal Na+ intake because acute K+ losses are offset by subsequent renal K+ retention; (b) this compensatory K+ retention can be inhibited by aldosterone release which could account for the negative K+ balance seen during salt restriction; (c) the short-term kaliuretic response to frusemide is augmented by release of both ADH and aldosterone whereas changes in K+ balance over 3 days of frusemide are dependent on plasma aldosterone concentration.

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.

scholarly journals SAT-119 Mechanisms of (Pro)renin Receptor Expression in the Kidney of Dahl Salt-Sensitive Rats by High Salt Intake

2019 ◽  
Vol 4 (7) ◽  
pp. S55
Author(s):  
S. YAMAKOSHI ◽  
O. Ito ◽  
Y. Osaki ◽  
T. Nakamura ◽  
T. Kazuhiro ◽  
...  
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Receptor Expression ◽  
High Salt Intake

scholarly journals Salt-sensitive splice variant of nNOS expressed in the macula densa cells

2010 ◽  
Vol 298 (6) ◽  
pp. F1465-F1471 ◽  
Author(s):  
Deyin Lu ◽  
Yiling Fu ◽  
Arnaldo Lopez-Ruiz ◽  
Rui Zhang ◽  
Ramiro Juncos ◽  
...  
Keyword(s):  
Salt Intake ◽  
Splice Variants ◽  
Macula Densa ◽  
High Salt ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake

Neuronal nitric oxide synthase (nNOS), which is abundantly expressed in the macula densa cells, attenuates tubuloglomerular feedback (TGF). We hypothesize that splice variants of nNOS are expressed in the macula densa, and nNOS-β is a salt-sensitive isoform that modulates TGF. Sprague-Dawley rats received a low-, normal-, or high-salt diet for 10 days and levels of the nNOS-α, nNOS-β, and nNOS-γ were measured in the macula densa cells isolated with laser capture microdissection. Three splice variants of nNOS, α-, β-, and γ-mRNAs, were detected in the macula densa cells. After 10 days of high-salt intake, nNOS-α decreased markedly, whereas nNOS-β increased two- to threefold in the macula densa measured with real-time PCR and in the renal cortex measured with Western blot. NO production in the macula densa was measured in the perfused thick ascending limb with an intact macula densa plaque with a fluorescent dye DAF-FM. When the tubular perfusate was switched from 10 to 80 mM NaCl, a maneuver to induce TGF, NO production by the macula densa was increased by 38 ± 3% in normal-salt rats and 52 ± 6% ( P < 0.05) in the high-salt group. We found 1) macula densa cells express nNOS-α, nNOS-β, and nNOS-γ, 2) a high-salt diet enhances nNOS-β, and 3) TGF-induced NO generation from macula densa is enhanced in high-salt diet possibly from nNOS-β. In conclusion, we found that the splice variants of nNOS expressed in macula densa cells were α-, β-, and γ-isoforms and propose that enhanced level of nNOS-β during high-salt intake may contribute to macula densa NO production and help attenuate TGF.

scholarly journals High Salt Intake Increases Copeptin but Salt Sensitivity Is Associated with Fluid Induced Reduction of Copeptin in Women

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Irina Tasevska ◽  
Sofia Enhörning ◽  
Philippe Burri ◽  
Olle Melander
Keyword(s):  
Body Weight ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Dietary Salt ◽  
Urinary Volume ◽  
Salt Consumption ◽  
High Salt Intake ◽  
Low Salt ◽  
Induced Changes

This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurements of 24 h blood pressure, body weight, 24 h urinary volume, and fasting plasma copeptin were performed at high and low salt consumption. Copeptin increased after a high compared to low dietary salt consumption in all subjects 3,59 ± 2,28 versus 3,12 ± 1,95 (P= 0,02). Copeptin correlated inversely with urinary volume, at both low (r= −0,42;P= 0,001) and high (r= −0,60;P< 0,001) salt consumption, as well as with the change in body weight (r= −0,53;P< 0,001). Systolic salt sensitivity was inversely correlated with salt-induced changes of copeptin, only in females (r= −0,58;P= 0,017). As suppression of copeptin on high versus low salt intake was associated with systolic salt sensitivity in women, our data suggest that high fluid intake and fluid retention may contribute to salt sensitivity.

Cardiac sympathetic afferent stimulation induces salt-sensitive sympathoexcitation through hypothalamic epithelial Na+ channel activation

2015 ◽  
Vol 308 (5) ◽  
pp. H530-H539 ◽  
Author(s):  
Koji Ito ◽  
Yoshitaka Hirooka ◽  
Kenji Sunagawa
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Salt Intake ◽  
Receptor Activation ◽  
High Salt ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Tnf Α ◽  
Excitatory Responses

The cardiac sympathetic afferent (CSA), which plays an important role in heart-brain communication for sympathoexcitation, is stimulated in heart failure. Additionally, high salt intake leads to further sympathoexcitation due to activation of hypothalamic epithelial Na+ channels (ENaCs) in heart failure. In the present study, we stimulated the CSA in adult male mice by epicardial application of capsaicin and using ethanol as a control to determine whether CSA stimulation led to activation of hypothalamic ENaCs, resulting in salt-induced sympathoexcitation. Three days after capsaicin treatment, an upregulation of hypothalamic α-ENaCs, without activation of mineralocorticoid receptors, was observed. We also examined expression levels of the known ENaC activator TNF-α. Hypothalamic TNF-α increased in capsaicin-treated mice, whereas intracerebroventricular infusion of the TNF-α blocker etanercept prevented capsaicin-induced upregulation of α-ENaCs. To examine brain arterial pressure (AP) sensitivity toward Na+, we performed an intracerebroventricular infusion of high Na+-containing (0.2 M) artificial cerebrospinal fluid. AP and heart rate were significantly increased in capsaicin-treated mice compared with control mice. CSA stimulation also caused excitatory responses with high salt intake. Compared with a regular salt diet, the high-salt diet augmented AP, heart rate, and 24-h urinary norepinephrine excretion, which is an indirect marker of sympathetic activity with mineralocorticoid receptor activation, in capsaicin-treated mice but not in ethanol-treated mice. Treatment with etanercept or the ENaC blocker benzamil prevented these salt-induced excitatory responses. In summary, we show that CSA stimulation leads to an upregulation of hypothalamic α-ENaCs mediated via an increase in TNF-α and results in increased salt sensitivity.

scholarly journals High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

2014 ◽  
Vol 144 (10) ◽  
pp. 1571-1578 ◽  
Author(s):  
Isis A. Katayama ◽  
Rafael C. Pereira ◽  
Ellen P. B. Dopona ◽  
Maria H. M. Shimizu ◽  
Luzia N. S. Furukawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Receptor Activation ◽  
High Salt ◽  
Cardiomyocyte Hypertrophy ◽  
High Salt Intake

scholarly journals Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes

2019 ◽  
Vol 20 (1) ◽  
pp. 160 ◽  
Author(s):  
Myoungsook Lee ◽  
Sungbin Richard Sorn ◽  
Yunkyoung Lee ◽  
Inhae Kang
Keyword(s):  
Defense Mechanisms ◽  
Salt Intake ◽  
High Salt ◽  
Mitogen Activated Protein Kinase ◽  
Future Research ◽  
High Dose ◽  
Obesity Prevalence ◽  
Salt Loading ◽  
Lipogenic Genes ◽  
High Salt Intake

It is well known that high salt intake is associated with cardiovascular diseases including hypertension. However, the research on the mechanism of obesity due to high salt intake is rare. To evaluate the roles of salt on obesity prevalence, the gene expression of adipogenesis/lipogenesis and adipocytokines secretion according to adipocyte dysfunction were investigated in salt-loading adipocytes. High salt dose-dependently increased the expression of adipogenic/lipogenic genes, such as PPAR-γ, C/EBPα, SREBP1c, ACC, FAS, and aP2, but decreased the gene of lipolysis like AMPK, ultimately resulting in fat accumulation. With SIK-2 and Na+/K+-ATPase activation, salt increased the metabolites involved in the renin-angiotensin-aldosterone system (RAAS) such as ADD1, CYP11β2, and MCR. Increasing insulin dependent insulin receptor substrate (IRS)-signaling, resulting in the insulin resistance, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt-mTOR were activated but AMPK(Thr172) was depressed in salt-loading adipocytes. The expression of pro-inflammatory adipocytokines, TNFα, MCP-1, COX-2, IL-17A, IL-6, leptin, and leptin to adiponectin ratio (LAR) were dose-dependently increased by salt treatment. Using the inhibitors of MAPK/ERK, U0126, we found that the crosstalk among the signaling pathways of MAPK/ERK, Akt-mTOR, and the inflammatory adipogenesis can be the possible mechanism of salt-linked obesity. The possibilities of whether the defense mechanisms against high dose of intracellular salts provoke signaling for adipocytes differentiation or interact with surrounding tissues through other pathways will be explored in future research.

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