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.

Effect of prostaglandin inhibition on the hypertensive action of sodium-retaining steroids.

“…The vascular changes produced by DOCA-salt in rats appear to be independent of potassium balance. 34 Vascular and renal prostaglandins have been implicated as modulating factors of blood pressure in a number of species. Prostaglandin (PG) IE, and I a are potent vasodilators.…”

Hyperpotassemia and Bradycardia in a Bedridden Elderly Woman with Selective Hypoaldosteronism Associated with Low Renin Activity

“…As may be anticipated by these findings (4,10) (3.8-4.3 g/dL) in the present patient. It has been described in previous reports (7,8,10,(12)(13)(14)(15)(16)(17)(18)(19) (8,15,16,18,20). The impairment of this direct effect of PGE2 on potassium excretion might also play a role in reduced potassium excretion, observed with NSAID administration (8,15,16,18).…”

The pressor actions of noradrenaline and angiotension II in chronic autonomic failure treated with indomethacin.

“…It is known, however, that even in the presence of autonomic degeneration plasma renin activity in the lying position is often normal (Bannister, Sever & Gross, 1977). As expected, indomethacin decreased plasma renin levels, (Speckart et al, 1977). A decrease in plasma renin activity could also contribute to the failure of indomethacin to prevent a fall in blood pressure on standing.…”

“…Although in all cases the log dose response curves after indomethacin lay to the left of that before indomethacin, only for 1 patient (case 2, Figure 2) was this shift marked. Indomethacin increases the pressor responsiveness to angiotensin II in nonnal man (Guthrie et al, 1976;Speckart, Zia, Zipser & Horton, 1977). However.…”