Low-salt diet enhances vascular reactivity and Ca(2+) entry in pregnant rats with normal and reduced uterine perfusion pressure.
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Salt moderation is often recommended to prevent excessive increases in blood pressure during pregnancy, particularly in women who are prone to pregnancy-induced hypertension; however, the vascular effects of low dietary salt intake during pregnancy are unclear. We investigated whether a low-salt diet during pregnancy alters the mechanisms of vascular smooth muscle contraction. Active stress and (45)Ca(2+) influx were measured in endothelium-denuded aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either a normal-sodium (NS, 1% NaCl) or low-sodium diet (LS, 0.2% NaCl) for 7 days. The mean arterial pressure was as follows: virgin/NS 108 +/- 8, virgin/LS 117 +/- 7, pregnant/NS 102 +/- 3, pregnant/LS 117 +/- 4, RUPP/NS 119 +/- 3, and RUPP/LS 133 +/- 6 mm Hg. Phenylephrine (Phe) caused concentration-dependent increases in active stress and (45)Ca(2+) influx that were greater in RUPP rats than in normal pregnant or virgin rats and were enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. High KCl (16 to 96 mmol/L), which stimulates Ca(2+) entry from the extracellular space, also caused increases in active stress that were greater in RUPP than in normal pregnant, in pregnant/LS than in pregnant/NS, and in RUPP/LS than in RUPP/NS rats. The Phe-induced (45)Ca(2+) influx--active stress relation was greater in RUPP/NS than in pregnant/NS and was enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. In Ca(2+)-free (2 mmol/L ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetra-acetic acid) Krebs, stimulation of intracellular Ca(2+) release by Phe (10(-5) mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. Thus, a low-salt diet in pregnant and RUPP rats is associated with increases in vascular reactivity that involves Ca(2+) entry from the extracellular space but not Ca(2+) release from the intracellular stores. The enhancement of the Phe-induced Ca(2+) influx--active stress relation in pregnant and RUPP rats on a low-salt diet suggests activation of other vascular contraction mechanisms in addition to Ca(2+) entry. Although it is difficult to extrapolate the experimental data in rats to clinical data in women, the increased vascular reactivity and Ca(2+) entry and the possible enhancement of additional vascular contraction mechanisms with a low-salt diet suggest that reduction of dietary salt intake should be carefully monitored during pregnancy and pregnancy-induced hypertension. (+info)
Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading.
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To determine the extent to which dietary sodium modulates aldosterone-induced cardiovascular damage, and to determine whether increased dietary potassium can prevent this damage, we used the Nomega-nitro-L-arginine methyl ester (L-NAME)/angiotensin II (Ang II) rat model of cardiac injury. This model is dependent on the presence of aldosterone for the occurrence of myocardial damage. Two sets of experiments were performed. In the first set, the following groups were studied: (1) 1% NaCl to drink (control group); (2) L-NAME/Ang II with water to drink (low salt group); (3) L-NAME/Ang II/1% NaCl (high salt group); (4) L-NAME/Ang II/1% NaCl/eplerenone (eplerenone group). Systolic blood pressure increased similarly in all groups compared with controls. Compared with the controls, the high salt group, but not the low salt or eplerenone groups, developed significant myocardial damage. In the second set of experiments three groups of animals were studied: (1) L-NAME/Ang II/1%NaCl (high salt group) (2) L-NAME/Ang II/1%NaCl/eplerenone (eplerenone group), and (3) L-NAME/Ang II/1%NaCl with an extra 1% KCl in food (high dietary potassium group). Eplerenone, but not dietary potassium supplementation, prevented the development of cardiac damage. Thus, mineralocorticoid receptor antagonist treatment and low sodium diet were effective in preventing cardiac damage, which suggests that a minimal level of aldosterone and a moderately high sodium diet are both required for the development of the cardiovascular damage in the L-NAME/Ang II model. The inability of potassium supplementation to reduce myocardial damage suggests that eplerenone's protective effect is not due to its potassium-sparing ability, but is rather related to some other feature of its selective aldosterone antagonism. (+info)
Enhanced responses of blood pressure, renal function, and aldosterone to angiotensin I in the DD genotype are blunted by low sodium intake.
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Angiotensin-converting enzyme (ACE) activity is increased in the DD genotype, but the functional significance for renal function is unknown. Blunted responses of BP and proteinuria to ACE inhibition among DD renal patients during periods of high sodium intake were reported. It was therefore hypothesized that sodium status affects the phenotype in the ACE I/D polymorphism. The effects of angiotensin I (AngI) and AngII among 27 healthy subjects, with both low (50 mmol sodium/d) and liberal (200 mmol sodium/d) sodium intakes, were studied. Baseline mean arterial pressure (MAP) values, renal hemodynamic parameters, and renin-angiotensin system parameters were similar for all genotypes with either sodium intake level. With liberal sodium intake, the increases in MAP, renal vascular resistance, and aldosterone levels during AngI infusion (8 ng/kg per min) were significantly higher for the DD genotype, compared with the ID and II genotypes (all parameters presented as percent changes +/- 95% confidence intervals), with mean MAP increases of 22 +/- 2% (DD genotype), 13 +/- 5% (ID genotype), and 12 +/- 6% (II genotype) (P < 0.05), mean increases in renal vascular resistance of 100.1 +/- 19.7% (DD genotype), 73.0 +/- 16.3% (ID genotype), and 63.2 +/- 16.9% (II genotype) (P < 0.05), and increases in aldosterone levels of 650 +/- 189% (DD genotype), 343 +/- 71% (ID genotype), and 254 +/- 99% (II genotype) (P < 0.05). Also, the decrease in GFR was more pronounced for the DD genotype, with mean decreases of 17.9 +/- 4.7% (DD genotype), 8.8 +/- 3.4% (ID genotype), and 6.4 +/- 5.9% (II genotype) (P < 0.05). The effective renal plasma flow, plasma AngII concentration, and plasma renin activity values were similar for the genotypes. In contrast, with low sodium intake, the responses to AngI were similar for all genotypes. The responses to AngII were also similar for all genotypes, with either sodium intake level. In conclusion, the responses of MAP, renal hemodynamic parameters, and aldosterone concentrations to AngI are enhanced for the DD genotype with liberal but not low sodium intake. These results support the presence of gene-environment interactions between ACE genotypes and dietary sodium intake. (+info)
Calcium diglutamate improves taste characteristics of lower-salt soup.
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OBJECTIVE: : To ascertain (1) whether the taste characteristics of a conventionally-salted (150 mM NaCl) soup can be reproduced in soups of substantially lower NaCl level with the help of added glutamate, and (2) whether calcium diglutamate (CDG) is equivalent to monosodium glutamate (MSG) in its effect on the taste of soup. DESIGN: : Cross-sectional, with multiple measurements on each subject. SETTING: : Healthy university students. SUBJECTS: : A total of 107 volunteers, recruited by on-campus advertising. METHODS: : Subjects tasted 32 soups, with all possible combinations of four NaCl concentrations (0-150 mM), four glutamate levels (0-43 mM), and two glutamate types (MSG, CDG). MAIN OUTCOME MEASURES: : Ratings of each soup on six scales (liking, flavour-intensity, familiarity, naturalness of taste, richness of taste, saltiness). RESULTS: : A 50 or 85 mM NaCl soup with added CDG or MSG is rated as high as, or higher than, a 150 mM NaCl soup free of added glutamate on five of the six scales (the exception being saltiness). CDG and MSG have equivalent effects. CONCLUSIONS: : Addition of glutamate allows substantial reductions in Na content of soup, without significant deterioration of taste. CDG and MSG have equivalent effects, but use of CDG permits a greater reduction in Na intake. (+info)
The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis.
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Hypertension is associated with impaired fibrinolysis. Both angiotensin receptor blockers (ARB) and the DASH (Dietary Approaches to Stop Hypertension) diet effectively lower blood pressure in hypertensive patients. Some evidence suggests that treatment with ARBs could increase fibrinolysis, however, data is conflicting. The impact of the DASH diet on fibrinolytic parameters is not known. Fifty-five hypertensive participants (35 African-American, 20 white) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet. The diets did not differ in sodium content (approximately 3 g/day). Within each diet, individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind, cross-over fashion. Tissue plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1) activity and plasma renin activity (PRA) were measured at the end of a 2-week run-in period on the control diet and after each treatment period. The DASH diet did not affect markers of fibrinolysis. Losartan significantly lowered t-PA antigen levels (-1.8 ng/mL, P = 0.045), but had no effect on t-PA or PAI-1 activities. This effect was more pronounced in whites (-4.1 ng/mL (P = 0.003)) compared with African-Americans (-0.3 ng/mL (P = 0.7), P-interaction = 0.03). Results were not materially affected by adjustment for basline values or changes in blood pressure. This study demonstrates that losartan reduces t-PA antigen levels in white, but not African-American hypertensive individuals. In contrast, the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans. (+info)
Salt-sensitivity of proximal reabsorption alters macula densa salt and explains the paradoxical effect of dietary salt on glomerular filtration rate in diabetes mellitus.
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GFR varies inversely with dietary NaCl in patients with early type I diabetes and in streptozotocin (STZ)-diabetic rats. To explain this paradox within the laws of physiology, it was hypothesized that it results from heightened sensitivity of the diabetic proximal tubule to dietary salt because changes in proximal reabsorption (Jprox) elicit reciprocal adjustments in GFR through the normal actions of tubuloglomerular feedback (TGF). Micropuncture was done in rats after 5 wk of moderately hyperglycemic STZ-diabetes and 1 wk of different NaCl diets. First, single-nephron GFR (SNGFR) and early distal tubular Na(+), Cl(-) and K(+) concentration (representing the TGF signal) were measured by collecting from early distal nephrons. In nondiabetics, dietary salt did not affect SNGFR or the TGF signal. In diabetics, the TGF signal varied directly with dietary salt while SNGFR varied inversely with dietary salt. Next, Jprox was measured by collecting from late proximal tubules. To control for different SNGFR, SNGFR was manipulated by perfusing Henle's loop to alter TGF activity. Controlling for SNGFR, dietary salt did not affect Jprox in nondiabetics but exerted a major inverse impact on Jprox in diabetics. In conclusion, normal rats acclimate to dietary NaCl by primarily adjusting transport downstream of the macula densa. In contrast, diabetes renders reabsorption in the proximal tubule sensitive to dietary NaCl with subsequent effects on the TGF signal. This explains the paradoxical effect of dietary NaCl on GFR in early diabetes. (+info)
Subclinical renal injury induced by transient cyclosporine exposure is associated with salt-sensitive hypertension.
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Cyclosporine use is highly associated with the development of salt-sensitive hypertension. We hypothesized that subtle renal injury induced by cyclosporine could lead to salt sensitivity. Cyclosporine nephropathy was induced by treatment for 4 weeks with cyclosporine (15 mg/kg/day) on a low sodium (0.05%) diet, followed by stopping cyclosporine and placement on a high sodium (4%) diet for 4 additional weeks. Control groups included a group treated with cyclosporine (15 mg/kg/day) on a normal salt diet in which nephropathy does not develop, and a vehicle-treated group. A fourth group received half-dose of cyclosporine (8 mg/kg/day) on a low sodium diet, which results in mild nephropathy. Biopsies were obtained at the end of the cyclosporine administration (4 week) and at sacrifice (8 week), and blood pressure and renal function were measured. Rats treated with cyclosporine for 4 weeks on a low sodium diet developed classic features of tubulointerstitial disease and arteriolopathy; these changes were absent in the cyclosporine/normal salt group and in the vehicle group. At 4 weeks, all groups were switched to a high salt diet; only the rats with nephropathy developed hypertension. The degree of hypertension correlated closely with the degree of tubulointerstitial injury (r=0.85) and with the severity of the arteriolopathy (r=0.9) (p<0.0.1). Importantly, renal function (creatinine clearance) was normal in all groups at 8 weeks, documenting that the hypertension could not be attributed to cyclosporine-mediated alterations in glomerular filtration rate (GFR). One mechanism by which cyclosporine induces hypertension is the induction of subtle renal microvascular and tubulointerstitial disease. This mechanism is not dependent on GFR and may persist even after the cyclosporine is discontinued. (+info)
Effect of renin-angiotensin system activation by dietary sodium restriction and upright position on plasma leptin concentration in patients with essential hypertension.
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BACKGROUND: Both leptin and the renin-angiotensin system (RAS) are involved in the regulation of arterial blood pressure. This study was undertaken to assess the relationship between RAS and plasma leptin concentration in hypertensive patients under conditions of normal and restricted sodium supply and upright position. MATERIAL/METHODS: In 31 patients with essential hypertension (EHP - 14 F, 17 M, age 44I14 years, BMI 29.3I6.4 kg/m2) and 8 healthy subjects (NHS - 4 F, 4 M, age 37(17 years, BMI 25.3I6.6 kg/m2) plasma leptin concentration, plasma renin activity (PRA), and 24-hour urinary sodium excretion (UNa) were evaluated twice: first on a diet containing 100-120 mmol sodium per day and after 8 hours overnight bed rest, and a second time after 3 days of dietary sodium restriction (10-20 mmol daily) and 3 hours in upright position. RESULTS: Dietary sodium restriction and upright position was followed by a significant increase in PRA and decrease of UNa. By contrast, plasma leptin concentration showed a moderate decrease both in EHP and NHS. No significant correlation was found between PRA and plasma leptin concentrations in either of the groups examined. CONCLUSIONS: From the results obtained in this study we may conclude that dietary sodium restriction and upright position exerts only a moderate effect on plasma leptin concentration, in contrast to PRA, in both hypertensive and normotensive subjects. (+info)