The effect of indomethacin and other anti-inflammatory drugs on the renin- angiotensin system

of indomethacin, 9 and 18 mg/kg, to two different groups of rabbits was followed 6 h later by a significant de-crease in plasma renin activity, and these levels were not increased by hemorrhage. The administration of 2 mg/kg of indomethacin did not alter the basal levels of plasma renin activity, but it was effective in diminish-ing the peripheral increase of renin produced by hemor-rhage. Similar effects were obtained in other groups of rabbits treated with 9 mg/kg of meclofenamate or 18 mg of aspirin. The lowering effect of indomethacin on plasma renin activity is not specifically related to hemor-rhage because it also prevented the increase in plasma renin activity elicited by 5 mg/kg of furosemide. Further studies showed that indomethacin did not exert any significant effect in vivo on the plasma level of renin substrate or on the generation of angiotensin from normal plasma by exogenous renin. And indo-methacin did not interfere with the binding capacity of anti-angiotensin I for angiotensin I in the radioimmuno-assay reaction or with the in vitro formation of angio-tensin from hog renin-nephrectomized rabbit plasma reaction. The results thus indicate that the lowering ef-fect of indomethacin on plasma renin activity is due to the interference with renal renin release. That this effect may be related to the blockade of prostaglandin synthesis is suggested by the similar effect exhibited by other blockers of prostaglandin synthesis