Proximal sodium reabsorption: An independent determinant of blood pressure response to salt.
(49/903)
The purpose of this study was to evaluate the contribution of renal sodium handling by the proximal tubule as an independent determinant of blood pressure responsiveness to salt in hypertension. We measured blood pressure (BP), renal hemodynamics, and segmental renal sodium handling (with lithium used as a marker of proximal sodium reabsorption) in 38 hypertensive patients and 27 normotensive subjects (15 young and 12 age-matched) on a high and low sodium diet. In control subjects, changing the diet from a low to a high sodium content resulted in no change in BP and increases in glomerular filtration rate (P<0.05), renal plasma flow (P<0.05), and fractional excretion of lithium (FE(Li), P<0.01). In hypertensive patients, comparable variations of sodium intake induced an increase in BP with no change in renal hemodynamics and proximal sodium reabsorption. When analyzed by tertiles of their BP response to salt, salt-insensitive hypertensive patients of the first tertile disclosed a pattern of adaptation of proximal sodium reabsorption comparable to that of control subjects, whereas the most salt-sensitive patients of the third tertile had an inverse pattern with a high FE(Li) on low salt and a lower FE(Li) on high salt, suggesting an inappropriate modulation of proximal sodium reabsorption. The BP response to salt correlated positively with age (r=0.34, P=0.036) and negatively with the changes in FE(Li) (r=-0.37, P=0.029). In a multivariate analysis, the changes in FE(Li) were significantly and independently associated with the salt-induced changes in BP. These results suggest that proximal sodium reabsorption is an independent determinant of the BP response to salt in hypertension. (+info)
Regulation of DRA and AE1 in rat colon by dietary Na depletion.
(50/903)
Two distinct Cl/anion exchange activities (Cl/HCO(3) and Cl/OH) identified in apical membranes of rat distal colon are distributed in cell type-specific patterns. Cl/HCO(3) exchange is expressed only in surface cells, whereas Cl/OH exchange is localized in surface and crypt cells. Dietary Na depletion substantially inhibits Cl/HCO(3) but not Cl/OH exchange. We determined whether anion exchange isoforms (AE) and/or downregulated in adenoma (DRA) are expressed in and related to apical membrane anion exchanges by examining localization of AE isoform-specific and DRA mRNA expression in normal and Na-depleted rats. Amplification of AE cDNA fragments by RT-PCR with colonic mRNA as template indicates that AE1 and AE2 but not AE3 mRNAs are expressed. In situ hybridization study revealed that AE1 mRNA is expressed predominantly in surface but not crypt cells. In contrast, AE2 polypeptide is expressed in basolateral membranes and DRA protein is expressed in apical membranes of both surface and crypt cells. AE1 mRNA is only minimally present in proximal colon, and DRA mRNA abundance is similar in distal and proximal colon. Dietary Na depletion reduces AE1 mRNA abundance but did not alter DRA mRNA abundance. This indicates that AE1 encodes surface cell-specific aldosterone-regulated Cl/HCO(3) exchange, whereas DRA encodes aldosterone-insensitive Cl/OH exchange. (+info)
Deoxycorticosterone suppresses the effects of losartan in nitric oxide-deficient hypertensive rats.
(51/903)
Chronic inhibition of the renin angiotensin system prevents increased BP and renal injury in N(G)-nitro-L-arginine methyl ester (L-NAME) hypertension. However, a relationship between plasma renin activity and the protective effect of chronic angiotensin II (Ang II) blockade has not been established. With this background, this study was undertaken to evaluate how the chronic administration of deoxycortisone acetate (DOCA) modifies the effects of losartan on BP, renal injury, and other variables in L-NAME hypertensive rats. The following groups were used: Control, DOCA, L-NAME, L-NAME + losartan, L-NAME + DOCA, and L-NAME + DOCA + losartan. Tail systolic BP was measured twice a week. After 4-wk evolution, mean arterial pressure and metabolic, morphologic, and renal variables were measured. The final mean arterial pressure values were 116 +/- 6 mmHg for control, 107 +/- 2 mmHg for DOCA, 151 +/- 5 mmHg for L-NAME, 123 +/- 2 mmHg for L-NAME + losartan, 170 +/- 3 mmHg for L-NAME + DOCA, and 171 +/- 5.5 mmHg for L-NAME + DOCA + losartan. Losartan prevented microalbuminuria, hyaline arteriopathy, and glomerulosclerosis of L-NAME hypertension but was ineffective in L-NAME + DOCA-treated rats. Plasma protein was significantly reduced in the L-NAME + DOCA group when compared with control and L-NAME groups, whereas no significant differences were observed in the other groups. Plasma renin activity was suppressed in the DOCA (0.55 +/- 0.2) and L-NAME + DOCA (0.60 +/- 10.2) groups but unsuppressed in the L-NAME + DOCA + losartan group (5.8 +/- 1). The conclusion is that DOCA blocks the preventive effect of losartan on the increased BP and renal injury of L-NAME hypertension, which suggests that DOCA transforms L-NAME hypertension into an Ang II-independent model of hypertension. These data also suggest that losartan prevents L-NAME hypertension by blocking the activity of systemic Ang II. (+info)
Diet and asthma.
(52/903)
The role of food intolerance in asthma is well recognized, and where food avoidance measures are instituted considerable improvement in asthma symptoms and in reduction in drug therapy and hospital admissions can result. These benefits may have a greater impact in those patients with greater symptoms. However, the promise of such benefits should not result in an approach which ignores inhaled drug therapy, or in a dietary regime which is inappropriate in the face of mild symptoms. Whilst sub-optimal intake of dietary nutrients is also a recently recognized potential risk factor for asthma, available data are insufficient to implicate any as casual. A number of studies have sought to establish the role of the antioxidant vitamins, A, C and E and selenium, yet others of the elements sodium and magnesium. Sub-optimal nutrient intake may enhance asthmatic inflammation, consequently contributing to bronchial hyperreactivity. Prospective studies of supplementation therapy are needed to confirm this. (+info)
Salt, blood pressure, and human health.
(53/903)
The positive relation of sodium intake and blood pressure, first recognized a century ago, has been well established in ecological, epidemiological, and experimental human studies. Equally well established is the association of increasing blood pressure and cardiovascular morbidity and mortality. Indeed, the pharmacological capacity to reduce blood pressure has produced one of the great public health accomplishments of the 20th century. These two facts-the positive relation of blood pressure to strokes and heat attacks and the positive association of sodium intake to blood pressure-underlie the hypothesis that a reduction in sodium intake, by virtue of its hypotensive effect, might prevent strokes and heart attacks. Moreover, even if the effect on blood pressure were in the range of a 1- to 2-mm Hg decline in blood pressure for every 75- to 100-mmol difference in sodium intake, the impact of such a change, applied to the whole population, would be enormous. The problem with this appealing possibility is that a reduction in salt consumption of this magnitude has other-and sometimes adverse-health consequences. The question, therefore, is whether the beneficial hypotensive effects of sodium restriction will outweigh its hazards. Unfortunately, few data link sodium intake to health outcomes, and that which is available is inconsistent. Without knowledge of the sum of the multiple effects of a reduced sodium diet, no single universal prescription for sodium intake can be scientifically justified. (+info)
Concerted action of dopamine on renal and intestinal Na(+)-K(+)-ATPase in the rat remnant kidney.
(54/903)
The present study evaluated renal and intestinal adaptations in sodium handling in uninephrectomized (Unx) rats and the role of dopamine. Two weeks after uninephrectomy, the remnant kidney in Unx rats weighed 33 +/- 2% more than the corresponding kidney in sham-operated (Sham) animals. This was accompanied by increases in urinary levels of dopamine and major metabolites [3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid] and increases in maximal velocity values (169 vs. 115 nmol. mg protein(-1). 15 min(-1)) for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine. High salt (HS) intake increased (P < 0.05) the urinary excretion of dopamine and DOPAC in Unx and Sham rats. However, the urinary levels of L-3,4-dihydroxyphenylalanine, dopamine, and DOPAC in Sham rats during HS intake were lower than in Unx rats. Blockade of dopamine D(1) receptors (Sch-23390, 2 x 30 microg/kg) reduced the urinary excretion of sodium in Unx (31% decrease) more pronouncedly than in Sham (19% decrease) rats. However, inhibition of renal Na(+)-K(+)-ATPase activity by dopamine was of similar magnitude in Unx and Sham rats. In parallel, it was observed that uninephrectomy resulted in a significant reduction in jejunal sodium absorption and Na(+)-K(+)-ATPase activity in jejunal epithelial cells. In jejunal epithelial cells from Sham rats, dopamine (1 microM) failed to inhibit Na(+)-K(+)-ATPase activity, whereas in Unx rats it produced a significant reduction. It is concluded that uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. Furthermore, it is suggested that decreased jejunal absorption of sodium may take place in response to partial renal ablation, as an example of renal-intestinal cross talk. (+info)
Dietary potassium and magnesium supplementation in cyclosporine-induced hypertension and nephrotoxicity.
(55/903)
BACKGROUND: Cyclosporine A (CsA)-induced hypertension and nephrotoxicity are aggravated by high sodium intake. Accumulating evidence suggests that potassium and magnesium supplementation could protect against the detrimental effects of dietary salt. In the present study, we tested the hypothesis of whether concurrent supplementation with potassium and magnesium could protect against the development of CsA-induced hypertension and nephrotoxicity more effectively than supplementation with one mineral alone. METHODS: Eight-week-old spontaneously hypertensive rats (SHRs) were divided into four groups (N = 10 in each group): (1) CsA group (5 mg/kg subcutaneously) receiving high-sodium diet (Na 2.6%, K 0.8%, Mg 0.2% wt/wt); (2) CsA group receiving a high-sodium, high-potassium diet (Na 2.6%, K 2.4%, Mg 0.2%); (3) CsA group receiving high-sodium, high-magnesium diet (Na 2.6%, K 0.8%, Mg 0.6%); and (4) CsA group receiving high-sodium, high-potassium, high-magnesium diet (Na 2.6%, K 2.4%, Mg 0.6%). RESULTS: CsA induced severe hypertension and deteriorated renal functions in SHRs on high-sodium diet. Histologically, the kidneys showed severe thickening of the media of the afferent artery with fibrinoid necrosis. Potassium supplementation lowered blood pressure (198 +/- 5 vs. 212 +/- 2 mm Hg, P < 0.05) and partially prevented the development of proteinuria (-25%, P < 0.05). Magnesium supplementation decreased blood pressure to the same extent but improved renal functions more effectively than potassium. The greatest protection against CsA toxicity was achieved when dietary potassium and magnesium supplementations were combined. Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, a marker for renal proximal tubular damage, increased progressively in CsA-treated SHRs on the high-sodium diet. Neither potassium nor magnesium influenced urinary NAG excretion. We also estimated the activity of the renal dopaminergic system by measuring 24-hour urinary dopamine excretion rates. CsA suppressed the renal dopaminergic system during high-sodium diet. Magnesium supplementation, alone and in combination with potassium, protected against the development of renal dopaminergic deficiency in CsA-treated SHRs on high-sodium diet. Magnesium supplementation increased plasma-free ionized magnesium (iMg) and bone magnesium by 50 and 16%, respectively. CONCLUSIONS: Our findings indicate that both potassium and magnesium supplementations showed beneficial effects against CsA-induced hypertension and nephrotoxicity. The protective effect of magnesium clearly exceeded that of potassium. The greatest protection against CsA toxicity was achieved when potassium and magnesium were combined. We also provide evidence that the development of CsA-induced glomerular, tubular, and vascular lesions are associated with renal dopaminergic deficiency. (+info)
Regulation of potassium channel Kir 1.1 (ROMK) abundance in the thick ascending limb of Henle's loop.
(56/903)
The renal outer medullary potassium channel (ROMK) of the thick ascending limb (TAL) is a critical component of the counter-current multiplication mechanism. In this study, two new antibodies raised to ROMK were used to investigate changes in the renal abundance of ROMK with treatments known to strongly promote TAL function. These antibodies specifically recognized protein of the predicted size of 45 kD in immunoblots of rat kidney or COS cells transfected with ROMK cDNA. Infusion of 1-deamino-(8-D-arginine)-vasopressin (dDAVP), a vasopressin V2 receptor-selective agonist, for 7 d into Brattleboro rats resulted in dramatic increases in apical membrane labeling of ROMK in the TAL of dDAVP-treated rats, as assessed by immunocytochemical analyses. Using immunoblotting, a more than threefold increase in immunoreactive ROMK levels was observed in the outer medulla after dDAVP infusion. Restriction of water intake to increase vasopressin levels also significantly increased TAL ROMK immunolabeling and abundance in immunoblots. In addition, dietary Na(+) levels were varied to determine whether ROMK abundance was also affected under other conditions known to alter TAL transport. Rats fed higher levels of sodium, as either NaCl or NaHCO(3) (8 mEq/250 g body wt per d), exhibited significantly increased density of the 45-kD band, compared with the respective control animals. Moreover, in rats fed a low-NaCl diet (0.25 mEq/250 g body wt per d), a 50% decrease in band density for the 45-kD band was observed (relative to control rats fed 2.75 mEq/250 g body wt per d of NaCl). These results demonstrate that long-term adaptive changes in ROMK abundance occur in the TAL with stimuli that enhance transport by this segment. (+info)