Mechanism of sodium modulation of glomerular angiotensin receptors in the rat.

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Abstract

Specific binding of 125I-angiotensin to high affinity glomerular receptors varies directly with the level of dietary sodium. To investigate the mechanism of sodium regulation of glomerular angiotensin receptors, groups of Sprague-Dawley rats were maintained on one of three levels of sodium intake for at least 5 d: high sodium (7.39 meq/24 h), moderate sodium (0.88 meq/24 h), and low sodium diets (0.01 meq/24 h). An additional group was given low sodium diet with daily injections of furosemide (1 mg/kg i.p.). To dissociate the effects of dietary sodium from those of circulating angiotensin II levels on glomerular receptor regulation, a fifth group was placed on high sodium diet and given a continuous infusion of angiotensin via an implanted minipump (100 ng/min) for 21 d. There was a strong negative correlation (r = -0.98, P less than 0.01) between plasma angiotensin II and glomerular angiotensin receptor density. Dietary sodium, potassium, or water consumption did not correlate with angiotensin II receptor concentration. The affinity constant did not vary in any of the groups (2.33 +/- 0.30 X 10(8) M-1). The time course of sodium regulation of glomerular angiotensin II receptors was studied in rats switched from a moderate sodium to either a high sodium diet or a low sodium diet plus furosemide. Receptor density was unchanged at 24 h, varied directly with sodium intake for 1-5 d when induction was maximal, and remained constant for at least 21 d. The time course of receptor regulation closely paralleled changes in plasma angiotensin II. Additional studies were undertaken to demonstrate that glomerular angiotensin II receptors are down-regulated by circulating hormone. Rats maintained on moderate sodium intake were killed 2 min after the induction of anesthesia with pentobarbital (50 mg/kg i.p.) or by rapid decapitation. Despite a 50-fold elevation of plasma angiotensin II in anesthetized rats (424 +/- 154 vs. 8.6 +/- 1.0 pg/ml, P less than 0.001) angiotensin receptor density was unchanged (anesthetized, 1,016 +/- 126 vs. unanesthetized, 1,290 +/- 84 fmol/mg). The infusion of angiotensin II (100 mg/min) for 15 min or 2 h into anesthetized rats maintained on moderate sodium intake resulted in a 50% reduction in specific angiotensin binding that could not be reversed by the dissociation of endogenous angiotensin. These data are compatible with modulation of receptor density by circulating hormone and can not be accounted for by prior receptor occupancy.

Authors

A Bellucci, B M Wilkes