Effects of a salt-restricted diet on the intake of other nutrients.
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BACKGROUND: Salt restriction, recommended as the first-line treatment of hypertension, has been proposed to lead to deficiencies in intakes of some other nutrients. OBJECTIVE: The aim of this study was to investigate the effects of salt restriction for 20 wk on the intake of other nutrients in free-living subjects with mildly elevated blood pressure. DESIGN: Thirty-nine subjects (24 men, 15 women) aged 28-65 y with a mean daytime ambulatory diastolic blood pressure of 90-105 mm Hg and a diastolic blood pressure measured in a health care center of 95-115 mm Hg participated in the study. The subjects completed 4-d food records and their salt intake was measured by 24-h urinary sodium excretion. The subjects received both oral and written instructions from a clinical nutritionist on how to reduce their daily sodium chloride intake to <5 g/d but were instructed not to change their diet otherwise. The subjects were provided with low-salt bread during the salt-restriction period. RESULTS: Few changes were found in nutrient intakes. In men, total energy intake decreased by 1059 kJ/d and alcohol, potassium, and vitamin D intakes decreased, but there were no significant changes in energy-adjusted potassium and vitamin D intakes. In women, total potassium intake increased, but the potassium density of the diet remained unchanged. Total selenium intake and energy-adjusted intake of selenium both decreased significantly in women. CONCLUSIONS: Salt restriction can be undertaken in free-living hypertensive subjects without any untoward changes in the intake of other nutrients. (+info)
CyA-mediated renal interstitial and vascular lesions in the rat under low-sodium diet.
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Nephrotoxicity of CyA was analyzed histologically in rats fed a low-sodium diet. CyA was subcutaneously administered daily at a dose of 15 mg/kg for 10 or 35 days with or without prior uninephrectomy (UNT) in male Sprague-Dawley rats receiving a low-sodium diet (0.03% sodium). CyA-administered rats showed impaired renal function as well as tubulo-interstitial lesions, such as edema, tubular basement membrane changes, and tubular atrophy, in the cortex, especially in the subcapsular portion, within 10 days. On day 35, the tubulo-interstitial lesions were advanced with mild focal interstitial fibrosis. These lesions were mild in the UNT group compared to the non-UNT group. Immunohistochemically, CyA treatment caused an increase in number of renin-positive cells in the afferent arteriolar wall at juxtaglomerular area. These cells lost the expression of calponin, which is a marker of mature smooth muscle cells. In addition, in afferent arterioles and interlobular arteries, electron-dense fibrous bodies were found in the smooth muscle cells on days 10 and 35. Immunoelectron microscopically, these bodies showed scattered positive staining for calponin and alpha-actinin, were negative or only peripherally positive for alpha-SMA and vimentin, and were completely negative for desmin. This study revealed that CyA could cause interstitial lesions starting in the subcapsular portion of the renal cortex and vascular lesions of the preglomerular artery. Increases in number of renin granules and formation of cytoplasmic fibrous bodies in smooth muscle cells could be the forerunner of severe arteriolar wall damage. (+info)
CA-Repeat polymorphism in intron 1 of HSD11B2 : effects on gene expression and salt sensitivity.
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Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta-hydroxysteroid dehydrogenase cause apparent mineralocorticoid excess, a form of familial hypertension. Because the hypertension associated with AME is of the salt-sensitive type, it seemed possible that decreases in 11-HSD2 activity might be associated with salt sensitivity. To examine this, Italians with mild hypertension underwent a protocol consisting of a rapid intravenous saline infusion and subsequent furosemide diuresis. To determine whether there were genetic associations between HSD11B2 and salt sensitivity, 198 Italians were genotyped for a CA repeat polymorphism (11 alleles) in the first intron. Increased differences in mean arterial pressure between the sodium loaded and depleted states were correlated with shorter CA repeat length (R=0.214, P=0. 0025). The effect behaved as a recessive trait. This suggested that decreased HSD11B2 expression was associated with shorter CA repeat length. Furthermore, activity of renal 11-HSD2 as measured by an increase in the ratio of urinary-free cortisol/urinary-free cortisone was lower in 33 salt-sensitive subjects (urinary-free cortisol/urinary-free cortisone 0.89+/-0.04 [mean+/-SE]) compared with 34 salt-resistant subjects (0.71+/-0.04, P<0.001). However, when minigenes containing either 14 or 23 CA repeats were transfected into rabbit or human kidney cortical collecting duct cells, the construct with 14 repeats was instead expressed at levels 50% higher than those of the construct with 23 repeats, as determined by reverse transcription-polymerase chain reaction. We conclude that polymorphisms in HSD11B2 and decreased 11-HSD2 activity are associated with sensitivity to sodium loading, but a functional explanation for these associations remains to be elucidated. (+info)
Low-salt diet alters the phospholipid composition of rat colonocytes.
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The effect of low-salt diet on phospholipid composition and remodeling was examined in rat colon which represents a mineralocorticoid target tissue. To elucidate this question, male Wistar rats were fed a low-salt diet and drank distilled water (LS, low-salt group) or saline instead of water (HS, high-salt group) for 12 days before the phospholipid concentration and fatty acid composition of isolated colonocytes were examined. The dietary regimens significantly influenced the plasma concentration of aldosterone which was high in LS group and almost zero in HS group. Plasma concentration of corticosterone was unchanged. When expressed in terms of cellular protein content, a significantly higher concentration of phospholipids was found in LS group, with the exception of sphingomyelin (SM) and phosphatidylserine (PS). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accounted for more than 70% of total phospholipids in both groups. A comparison of phospholipid distribution in LS and HS groups demonstrated a higher percentage of PE and a small, but significant, decrease of PC and SM in LS group. The percentage of phosphatidylinositol (PI), PS and cardiolipin (CL) were not affected by mineralocorticoid treatment. With respect to the major phospholipids (PE, PC), a higher level of n-6 polyunsaturated fatty acids (PUFA) and lower levels of monounsaturated fatty acids were detected in PC of LS group. The increase of PUFA predominantly reflected an increase in arachidonic acid by 53%. In comparison to the HS group, oleic acid content was decreased in PC and PE isolated from colonocytes of the LS group. Our data indicate that alterations in phospholipid concentration and metabolism can be detected in rats with secondary hyperaldosteronism. The changes in phospholipid concentration and their fatty acid composition during fully developed effect of low dietary Na+ intake may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function. (+info)
Contribution of angiotensin-(1-7) to blood pressure regulation in salt-depleted hypertensive rats.
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We exposed 63 adult spontaneously hypertensive rats (SHR) and 10 (mRen-2)27 transgenic hypertensive rats to a 12-day regimen of either a normal diet (0.5%) or a low-salt diet (0.05%) to evaluate the hypothesis that the vasodepressor heptapeptide, angiotensin-(1-7) [Ang-(1-7)], buffers the pressor effects of angiotensin II during endogenous stimulation of the renin-angiotensin system. Catheters were inserted into a carotid artery and jugular vein under light anesthesia the day before the experiment. Separate groups of conscious instrumented SHR were given short-term infusions of an affinity-purified monoclonal Ang-(1-7) antibody or the neprilysin inhibitor SCH 39370. In addition, SHR and (mRen-2)27 rats were given the Ang-(1-7) receptor antagonist [D-Ala(7)]Ang-(1-7). Exposure to the low-salt diet increased plasma renin activity and elevated plasma levels of angiotensin I and angiotensin II in SHR by 81% and 68%, respectively, above values determined in SHR fed a normal salt diet. Concentrations of angiotensin I and angiotensin II were also higher in the kidney of salt-depleted SHR, whereas plasma and renal tissue levels of Ang-(1-7) were unchanged. Infusion of the Ang-(1-7) antibody produced dose-dependent pressor and tachycardic responses in salt-depleted SHR but no effect in SHR maintained on a normal-salt diet. A comparable cardiovascular response was produced in salt-depleted SHR given either SCH 39370 or [D-Ala(7)]Ang-(1-7). These agents had negligible effects on SHR fed a normal-salt diet. Blockade of Ang-(1-7) receptors produced a similar cardiovascular response in (mRen-2)27 transgenic hypertensive rats fed a low-salt diet. Injections of the heat-inactivated antibody or the subsequent infusion of the antibody to rats given [D-Ala(7)]Ang-(1-7) produced no additional effects. The data support the hypothesis that the hemodynamic effects of neurohormonal activation after salt restriction stimulate a tonic depressor action of Ang-(1-7). (+info)
Comparative study of the cardiovascular effects of losartan in normal and in water- and salt-depleted sheep.
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The cardiovascular effects of losartan, a non-peptidic angiotensin II (ANG II) receptor antagonist, were studied in sheep. Eight normotensive, conscious sheep were tested twice: first under normal conditions and second when subjected to water and electrolytic depletion (furosemide 5 mg/kg twice a day for 3 days). Intravenous injection of 30 mg/kg losartan lowered the mean arterial blood pressure (MABP) in both control and water- and electrolyte-depleted sheep alike. The maximal decrease in MABP was significantly greater in diuretic-treated sheep than in controls (20.0 +/- 2.7 vs 9.3 +/- 1.1 mmHg) and occurred earlier (8.0 +/- 3.3 min vs 12.1 +/- 2.9 min). The decrease in blood pressure was associated with tachycardia in both controls and diuretic-treated sheep (+5.5 +/- 1.8 vs +11.3 +/- 3.9 beats/min). The vasopressor response to 0.1 microg/kg ANG II administered 30 min after losartan was completely antagonized. Two hours after losartan administration, MABP was on the increase in all animals and ANG II receptor blockade was partially obliterated in control sheep. The more marked cardiovascular effects recorded in diuretic-treated sheep as compared to control animals were associated with an increased activation of the renin-angiotensin system (plasma renin concentration: 6.51 +/- 1.33 vs 1.42 +/- 0.37 ng angiotensin I/ml/hr). (+info)
Induction of apoptosis during development of hypertensive nephrosclerosis.
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BACKGROUND: As the biology of programmed cell death, or apoptosis, is clarified, a role for this process in the pathophysiology of organ dysfunction and fibrosis has been hypothesized. Hypertensive nephrosclerosis represents an important cause of end-stage renal disease. One model of the progressive, noninflammatory, sclerotic renal lesion of hypertension is the Dahl/Rapp salt-sensitive rat, which was examined in this study. METHODS: Male, Dahl/Rapp salt-sensitive (SS) and Sprague-Dawley rats were placed on either 0.3 or 8.0% NaCl diets for three weeks. Blood pressure was determined, and the kidneys were harvested for histochemical analysis and to obtain total RNA for RNase protection assays and total protein for Western blotting. RESULTS: An increase in apoptosis in the glomerular and tubular compartments was observed only in kidneys of SS rats on the high-salt diet. These findings occurred at a time when renal function was markedly impaired and irreversible changes in renal morphology developed. Temporally associated with this increase in apoptosis was augmented expression of pro-apoptotic molecules that included Fas, Bax, and Bcl-XS. CONCLUSIONS: The inappropriate shift in expression of proteins that facilitate apoptosis in the nephron, along with ongoing cell death that manifested at a time when renal function was deteriorating, supported an important role for this process in development of hypertensive nephrosclerosis. (+info)
Renal expression of constitutive NOS and DDAH: separate effects of salt intake and angiotensin.
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BACKGROUND: Nitric oxide (NO) is generated from NO synthase (NOS) isoforms. These enzymes can be inhibited by asymmetric dimethylarginine, which is inactivated by N(G)-N(G)-dimethylarginine dimethylaminohydrolase (DDAH). The neuroneal (nNOS) type I and endothelial (eNOS) type III constitutive NOS isoforms are expressed predominantly in the macula densa and microvascular endothelium of the renal cortex, respectively. DDAH is expressed at sites of NOS expression. Since NO may coordinate the renal responses to angiotensin II (Ang II) and changes in salt intake, we tested the hypothesis that salt intake regulates the expression of nNOS, eNOS and DDAH by Ang II acting on type 1 (AT(1)) receptors. METHODS: Groups (N = 6) of rats were adapted to low-salt (LS) or high-salt (HS) intakes for 10 days. Other groups of LS and HS rats received the AT(1) receptor antagonist losartan for six days (to test the effects of salt independent of AT(1) receptors). A further group of HS rats received an infusion of Ang II for six days (to test the effect of Ang II independent of salt intake). RESULTS: Compared with HS rats, there was a significant (P < 0.05) increase in LS rats of nNOS protein in kidney and immunohistochemical expression in the macula densa, and of eNOS protein expression and immunohistochemical expression in the microvascular endothelium, and of DDAH protein expression. Losartan prevented these effects of salt on the expression of eNOS or DDAH, both of which were also increased by Ang II infusions in HS rats. In contrast, losartan did not prevent the effects of salt on nNOS expression, which was unresponsive to Ang II infusion. The generation of NO(2)(-) released by slices of renal cortex, in the presence of saturating concentrations of L-arginine, was increased by LS, compared to HS, independent of losartan and by Ang II during HS. CONCLUSION: The expressions of eNOS in cortical microvascular endothelium and DDAH in kidney are enhanced by Ang II acting on AT(1) receptors. The expression of nNOS in the macula densa is enhanced by salt restriction independent of Ang II or AT(1) receptors. (+info)