The calciuric response to dietary salt of Dahl salt-sensitive and salt-resistant male rats.

BACKGROUND: There are conflicting reports regarding the effect of salt sensitivity on the calciuric response to salt, perhaps because of gender differences and different modes of salt administration. We tested the hypothesis that the calciuric response to dietary salt would not differ for male Dahl salt-sensitive (S) and salt-resistant (R) rats. METHOD: S and R rats were fed high- (80 g/kg) or low- (3 g/kg) salt diets for 3 weeks and urine (24 hour) was collected weekly. RESULTS: Urinary calcium excretion was up to 20-fold greater for S and R rats fed a high-salt diet (P < 0.001) than for S and R rats fed a low-salt diet and did not differ significantly between S and R rats. S rats, however, excreted calcium in significantly higher urine volumes (P< 0.001) during high salt intake and developed hypertension. Plasma parathyroid hormone concentrations of S and R rats did not differ during low salt intake and increased significantly to the same concentration after 3 weeks of high salt intake. CONCLUSIONS: We have previously reported that plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations of male S rats, but not male R rats, were drastically reduced by 3 weeks of high salt intake. These data suggest that salt-induced hypertension and salt-induced alterations in the vitamin D endocrine system of male S rats do not affect the calciuric response to dietary salt.

Gene expression profile in mouse myocardium after ischemia.

This study was designed to elaborate a molecular profile of expressed genes during ischemic injury to the mouse heart after surgical constriction of the left coronary artery without reperfusion. A mouse cDNA array containing 588 known genes was used to compare gene expression in heart RNA after 24-h ischemia with control tissue. Alterations in gene expression on the array were supported by relative reverse transcription-polymerase chain reaction analysis after timed periods of ischemia. Decreased levels of the cell cycle regulator p18ink4 and the oxidative responsive gene glutathione S-transferase were accompanied by an upregulation of the genes associated with cardiac muscle development, alpha-myosin heavy chain and fetal myosin alkali light chain. Other stress responses elicited by cardiac injury included an induction of Egr-1 and Egr-3 transcription factors, as well as the apoptotic regulator Bax. Altogether, these findings indicate that expression of genes associated with a fetal transcription program may be involved with the post ischemic remodeling process in heart ventricles.

Plasma 25-hydroxyvitamin D concentrations are inversely associated with blood pressure of Dahl salt-sensitive rats.

Dietary salt is a contributing factor to the development of hypertension in individuals who are salt-sensitive. The vitamin D endocrine system has been reported to modulate vascular structure and function. Since elderly hypertensive females with low plasma renin activity, typical of salt-sensitivity, had significantly lower 25-hydroxyvitamin D concentrations compared with normotensive elderly and young females, we have used Dahl salt-sensitive and salt-resistant rats fed high (80 g/kg diet) and low (3 g/kg diet) salt diets as models to examine the relationship between salt-sensitivity and 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D. Plasma 25-hydroxyvitamin D concentrations of salt-resistant rats were unaffected by a high salt diet, but plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats were significantly reduced within three weeks to lower than 25%. There was a negative association between plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats and the number of days that the rats were fed a high salt diet (r = -0.98, P < 0.02) and a positive association between blood pressure and the number of days that the rats were fed a high salt diet (r = 0.97, P < 0.05). An inverse relationship was found between plasma 25-hydroxyvitamin D concentrations and blood pressure (r = -0.99, P < 0.01). Spontaneously hypertensive rats did not have low plasma 25-hydroxyvitamin D concentrations, suggesting that reduction of plasma 25-hydroxyvitamin D concentration might be specific to salt-induced hypertension.

Exogenous 25-hydroxycholecalciferol does not attenuate salt-induced hypertension.

We have reported that an inverse relationship exists between blood pressure and plasma concentration of 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, for Dahl salt-sensitive rats fed a high salt diet. Plasma 25-hydroxyvitamin D concentrations decreased with time on the diet, as blood pressure increased. Experiments were conducted to determine whether the blood pressure increase of salt-sensitive rats fed a high salt diet could be attenuated by exogenous 25-hydroxycholecalciferol. Dahl salt-sensitive rats were fed a high salt diet and administered exogenous 25-hydroxycholecalciferol via subcutaneously implanted Alzet pumps. Exogenous 25-hydroxycholecalciferol (various doses from 28 to 80 microg/kg body weight-day) had no significant effect on the blood pressure of vitamin D-replete rats fed a high salt diet for 15 days. When exogenous 25-hydroxycholecalciferol (28 and 60 microg/day-kg body weight) was administered to vitamin D-depleted salt-sensitive rats, plasma 25-hydroxyvitamin D concentrations of the rats fed a low salt diet (26 +/- 2 and 59 +/- 6 nM) were proportional to the 25-hydroxycholecalciferol concentration in the pumps. Plasma 25-hydroxyvitamin D concentrations of the rats fed a high salt diet (18 +/- 1 and 23 +/- 3 nM) were not proportional to the 25-hydroxycholecalciferol concentration in the pumps, but were inversely proportional to the blood pressure of the rats. These data indicate no ameliorating effect of exogenous 25-hydroxycholecalciferol on salt-induced hypertension, but accelerated metabolism and/or clearance of 25-hydroxycholecalciferol in salt-induced hypertension.

The effects of oral and intraperitoneal administration of ethanol on the activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rats.

The activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases decreased significantly only in male rats, when rats of both sexes were fed a 2% sucrose solution containing 25% ethanol for six weeks. Sucrose (2%) activation of these enzymes was significant only in female rats. The daily administration of ethanol (5 g/kg body wt.) by intraperitoneal injection for two weeks significantly decreased the activities of these enzymes and eliminated the sex differences in the response to ethanol ingestion.

Evidence for renin in rat brain: differentiation from other reninlike enzymes.

We observed that unfractionated rat brain extract incubated with substrate at pH 6.0 yielded 12 times the quantity of angiotensin I as incubations at pH 7.4, but the enzyme activity measured at pH 6 was not primarily due to renin. To examine the existence of renin in brain, we used three methods of affinity chromatography (pepstatin-, renin-specific antibody-, and alpha-casein-Sepharose) to fractionate the angiotensin I-generating enzymes in the brain. 1) Brain extract applied to renin-specific column eluted a peak of angiotensin-releasing activity (ARA) that had a pH optimum of 6.0. This ARA was inhibited by antirenin antibody. Another peak of ARA with a pH optimum of 4 appeared in the nonbound fraction. This peak was not affected by antirenin antibody and had acid protease activity. 2) Pepstatin affinity column elution with lithium bromide yielded an early ARA peak (pH optimum 6.5), inhibited by antirenin antibody and a later peak (pH optimum 4.0) not inhibited by antirenin antibody. The latter contained acid protease activity. 3) alpha-Casein-Sepharose column also separated neutral proteases and immunoreactive renin from acid protease capable of generating angiotensin. In summary, rat brain contains a host of angiotensin I-generating enzymes that can be detected and separated as neutral and acid proteases and immunoreactive renin depending on the pH of the assay and conditions of purification. These findings indicate the presence of an enzyme with immunoidentity to renin in rat brain but do not imply local biosynthesis.