Decreased osteopontin expression in the rat kidney on a sodium deficient diet.
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Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney. (+info)
High dietary sodium chloride consumption may not induce body fluid retention in humans.
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A commonly accepted hypothesis is that a chronically high-sodium diet expands extracellular volume and finally reaches a steady state where sodium intake and output are balanced whereas extracellular volume is expanded. However, in a recent study where the main purpose was to investigate the role of natriuretic peptides under day-to-day sodium intake conditions (Heer M, Drummer C, Baisch F, and Gerzer R. Pflugers Arch 425: 390-394, 1993), our laboratory observed increases in plasma volume without any rise in extracellular volume. To scrutinize these results that were observed as a side effect, we performed a controlled, randomized study including 32 healthy male test subjects in a metabolic ward. The NaCl intake ranged from a low level of 50 meq NaCl/day to 200, 400, and 550 meq/day, respectively. Plasma volume dose dependently increased (P < 0.01), being elevated by 315 +/- 37 ml in the 550-meq-NaCl-intake group. However, in contrast to the increased plasma volume, comparable to study I, total body water did not increase. In parallel, body mass also did not increase. Mean corpuscular volume of erythrocytes, as an index for intracellular volume, was also unchanged. We conclude from the results of these two independently conducted studies that under the chosen study conditions, in contrast to present opinions, high sodium intake does not induce total body water storage but induces a relative fluid shift from the interstitial into the intravascular space. (+info)
Ouabain-sensitive H,K-ATPase functions as Na,K-ATPase in apical membranes of rat distal colon.
(27/721)
Na,K-ATPase activity has been identified in the apical membrane of rat distal colon, whereas ouabain-sensitive and ouabain-insensitive H,K-ATPase activities are localized solely to apical membranes. This study was designed to determine whether apical membrane Na,K-ATPase represented contamination of basolateral membranes or an alternate mode of H,K-ATPase expression. An antibody directed against the H, K-ATPase alpha subunit (HKcalpha) inhibited apical Na,K-ATPase activity by 92% but did not alter basolateral membrane Na,K-ATPase activity. Two distinct H,K-ATPase isoforms exist; one of which, the ouabain-insensitive HKcalpha, has been cloned. Because dietary sodium depletion markedly increases ouabain-insensitive active potassium absorption and HKcalpha mRNA and protein expression, Na, K-ATPase and H,K-ATPase activities and protein expression were determined in apical membranes from control and sodium-depleted rats. Sodium depletion substantially increased ouabain-insensitive H, K-ATPase activity and HKcalpha protein expression by 109-250% but increased ouabain-sensitive Na,K-ATPase and H,K-ATPase activities by only 30% and 42%, respectively. These studies suggest that apical membrane Na,K-ATPase activity is an alternate mode of ouabain-sensitive H,K-ATPase and does not solely represent basolateral membrane contamination. (+info)
Role of adrenal renin-angiotensin system in the control of aldosterone secretion in sodium-restricted rats.
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This study examined the effect of the pharmacological manipulation of adrenal renin-angiotensin system (RAS) on aldosterone secretion from in situ perfused adrenals of rats kept on a normal diet and sodium restricted for 14 days. Neither the angiotensin-converting enzyme inhibitor captopril nor the nonselective angiotensin II receptor antagonist saralasin and the AT(1) receptor-selective antagonist losartan affected basal aldosterone output in normally fed rats. In contrast, they concentration dependently decreased aldosterone secretion in sodium-restricted animals, with maximal effective concentration ranging from 10(-7) to 10(-6) M. Captopril (10(-6) M), saralasin (10(-6) M), and losartan (10(-7) M) counteracted aldosterone response to 10 mM K(+) in sodium-restricted rats but not in normally fed animals. Collectively, these findings provide evidence that adrenal RAS plays a role in the regulation of aldosterone secretion, but only under conditions of prolonged stimulation of zona glomerulosa probably leading to overexpression of adrenal RAS. (+info)
Reinforcement of arteriolar myogenic activity by endogenous ANG II: susceptibility to dietary salt.
(29/721)
The purpose of this study was to determine whether endogenous ANG II augments arteriolar myogenic behavior in striated muscle. Because circulating ANG II is decreased during high salt intake, we also investigated whether dietary salt could alter any influence of ANG II on myogenic behavior. Normotensive rats fed low-salt (0.45%, LS) or high-salt (7%, HS) diets were enclosed in a ventilated box with the spinotrapezius muscle exteriorized for intravital microscopy. Dietary salt did not affect resting arteriolar diameters. Microvascular pressure elevation by box pressurization caused greater arteriolar constriction in LS rats (up to 12 microm) than in HS rats (up to 4 microm). The ANG II-receptor antagonists saralasin and losartan attenuated myogenic responsiveness in LS rats but not HS rats. The bradykinin-receptor antagonist HOE-140 had no effect on myogenic responsiveness in LS rats but augmented myogenic responsiveness in HS rats. HOE-140 with the angiotensin-converting enzyme inhibitor captopril attenuated myogenic responsiveness to a greater extent in LS rats than in HS rats. We conclude that endogenous ANG II normally reinforces arteriolar myogenic behavior in striated muscle and that attenuated myogenic behavior associated with high salt intake is due to decreased circulating ANG II and increased local kinin levels. (+info)
Effects of resalination on intestinal glucose transport in chickens adapted to low Na+ intakes.
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In chickens, we have shown that intestinal absorption of glucose via apical SGLT1 and basolateral GLUT2 transport systems is affected by dietary Na+; low-Na+ adapted birds show a dramatic reduction of glucose transporters in both membranes in the rectum, an intermediate response in the ileum and no effects in the jejunum. We have now studied the effect of resalination of low-Na+ adapted chickens on glucose kinetics across SGLT1 (using -methyl-D-glucoside as substrate) and GLUT2 (using D-glucose) and on the specific binding of phlorizin and cytochalasin B, respectively. Twelve-week-old male Leghorn chickens were fed wheat and barley with drinking water containing either 150 mM NaCl (high-Na+ group) or 0. 015 mM (low-Na+ group) for 14 days (serum aldosterone: 242 +/- 6 pg ml-1 in the low-Na+ and 46 +/- 4 pg ml-1 in the high-Na+ group). On day 14, the low-Na+ group was either resalinated with an oral dose of NaCl (9 g (kg body wt)-1) or switched to the high-Na+ condition, for 1 week. Serum aldosterone measured 4 h, 1 day and 7 days after the change in NaCl intake fell to between 30 and 39 pg ml-1. The changes in apical -methyl-D-glucoside and basolateral D-glucose transport observed in the ileum and rectum of low-Na+ adapted animals were completely reversed by resalination within 4 h of NaCl administration to the level of values observed for high-Na+ adapted birds. The good correlation between the -methyl-D-glucoside and D-glucose Vmax and the SGLT1 and GLUT2 density, respectively, supports the view that the increase in apical and basolateral hexose transport found in the ileum and rectum of both groups of resalinated birds is due to an increase in the number of protein transporters. The rapid changes in the number of glucose transporters observed suggest that the target of the regulatory signal(s) involved are the mature enterocytes present in the villi rather than the developing enterocytes in the crypt. (+info)
Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets.
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Previous electrophysiological experiments on renal cortical collecting ducts indicated that dietary sodium intake and variations in aldosterone plasma levels regulate the abundance of functional epithelial Na channels (ENaC) in the apical plasma membrane. In mouse kidney we investigated by immunohistochemistry whether feeding for 3 wk a diet with high (3% Na) and low (0.05% Na) Na content influences the distribution pattern of ENaC. In mice of all experimental groups, ENaC was apparent in cells from the late portion of the distal convoluted tubule (DCT2) down to the medullary collecting duct (CD). In mice on a high-Na diet (plasma aldosterone: 40.8 +/- 2.0 ng/dl), the alpha-subunit was undetectable, and the beta- and gamma-ENaC were detected in the cytoplasm, but not in the apical plasma membrane of the cells. In contrast, in mice on a low-Na diet (plasma aldosterone: 93.6 +/- 9.3 ng/dl) all three ENaC subunits were displayed in the subapical cytoplasm and in the apical membrane of DCT2, connecting tubule (CNT), and, although less prominent, in cortical CD cells. Apical plasma membrane immunostaining progressively decreased along the cortical CD, simultaneously with increasing cytoplasmic staining for beta- and gamma-ENaC. Thus our data on mice adapted to moderately low and high Na intake suggest that regulation of ENaC function in vivo involves shifts of beta- and gamma-subunits from the cytoplasm to the apical plasma membrane and vice versa, respectively. The insertion of these subunits into the apical plasma membrane coincides with upregulation of the alpha-subunit and its insertion into the apical plasma membrane. (+info)
Roles of ANG II and bradykinin in the renal regional blood flow responses to ACE inhibition in sodium-depleted dogs.
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The relative contributions of ANG II and bradykinin (BK) to the renal regional blood flow responses during angiotensin-converting enzyme (ACE) inhibition remain unclear. This study was performed to evaluate renal cortical (CBF) and medullary blood flow (MBF) responses to intrarterial administration of enalaprilat (33 microg. kg(-1). min (-1)) after blockade of the ANG II AT(1 )receptors with candesartan (100 microg) in 7 dogs fed a low-salt diet (0.01%) for 5 days. Laser-Doppler flowmetry was used to measure relative changes in CBF and MBF. Candesartan alone increased CBF (+20 +/- 2%) and MBF (+22 +/- 7%). Enalaprilat infusion after candesartan administration resulted in further increases in both CBF (+21 +/- 5%) and MBF (+41 +/- 8%). However, the relative changes in MBF were significantly greater (P < 0.01) than those in CBF. Administration of the BK B(2) receptor blocker icatibant (300 microg) after enalaprilat returned CBF and MBF to values seen with candesartan alone. These data support a substantive role for BK potentiation during ACE inhibitor-induced renal vasodilation in dogs maintained on a low-sodium diet, with a relatively greater effect on MBF compared to CBF. (+info)