Effect of sodium balance and calcium channel-blocking drugs on plasma aldosterone responses to infusion of angiotensin II in normal subjects and patients with essential hypertension.

Abstract

To study the role of calcium movements in mediating the effects of sodium chloride on the response of plasma aldosterone to angiotensin II (AII), we administered calcium channel-blocking drugs (nifedipine and diltiazem) and calcium infusions to normal subjects during high and low sodium intakes before and after AII infusion. AII was also infused in 13 patients with essential hypertension eating a high sodium diet. In preliminary studies, the effects of nifedipine (20 mg, orally) on blood pressure, PRA, plasma aldosterone, and plasma cortisol concentrations were determined. Sensitivity to infused AII was calculated as the slope of the linear regression of the increase in plasma aldosterone as a function of the AII infusion rate (nanograms per dl/ng AII/kg X min). During sodium restriction (10 meq Na/day), both drugs significantly (P at least less than 0.05) reduced AII sensitivity. During the high sodium diet (200 meq Na/day), only diltiazem decreased AII sensitivity, and the reduction was less (P less than 0.05) than that during the low sodium diet. There was a significant (P less than 0.001) inverse correlation between the initial plasma aldosterone sensitivity to AII and the change in sensitivity induced by the calcium channel-blocking drugs in normal subjects (r = -0.89) and hypertensive patients (r = -0.70). Five hypertensive patients had greater than normal aldosterone sensitivity to AII, which was significantly (P less than 0.05) reduced by nifedipine. Calcium infusion increased the aldosterone sensitivity to AII during the low sodium diet, but not during the high sodium diet. The results suggest that in normal subjects, increased plasma aldosterone responses to AII induced by reduction in sodium intake are partially mediated by increased extracellular to intracellular calcium movements, since they are blocked by the structurally different calcium channel-blocking drugs nifedipine and diltiazem. In hypertensive patients eating a high sodium diet, increased aldosterone responses to AII infusion were blocked by nifedipine, indicating that they are at least partly mediated by increased extracellular to intracellular calcium flux.