The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man

Abstract

To investigate the possible interrelationship between the renin-angiotensin and prostaglandin systems, two groups of normal men were evaluated under conditions of varied sodium intake and after indomethacin, an inhibitor of prostaglandin synthesis. Eight subjects were placed on a 200 mEq Na diet and given 45 min infusions of prostaglandin A1 (PGA1) at 0.075 microng/kg/min and angiotensin II at 10 ng/kg/min on separate mornings. PGA1 produced a significant rise in both plasma renin activity (PRA) and aldosterone. Angiotensin II caused a similar rise in aldosterone. The patients were then placed on a 10-20 mEq Na diet and the infusions repeated. PGA1 again induced a further increase in both PRA and aldosterone. Angiotensin II produced the expected increase in aldosterone while PRA decreased. Body weight and 24 h sodium excretion were not different from control days on either diet. When indomethacin was administered to patients on the low sodium diet, PRA fell significantly and there was an increased pressor responsiveness to angiotensin. In a separate group of 4 patients on a low salt intake, basal PRA fell significantly during a 4 day period of indomethacin administration and returned to control values within 48 h after discontinuing the drug. These studies suggest that PGA1 infusions stimulate renin release independently of sodium balance. Inhibition of prostaglandin synthesis lowers PRA and increases pressor responsiveness to angiotensin. The data provide further evidence that vasodepressor prostaglandins may play a role in renin release and blood pressure homeostasis.