Inhibition of hydralazine-induced renin release by indomethacin in the rat

Abstract

Renal prostaglandins (PG) appear to mediate the release of renin due to activation of the intrarenal baroreceptor and stimulation of the renal sympathetic nerves. Since the vasodilator hydralazine is thought to stimulate renin release by both of these mechanisms, we examined the effect of indomethacin, a PG synthetase inhibitor, on hydralazine-induced renin release. Hydralazine increased the serum renin levels from 3.3 +/- 0.5 to 13.7 +/- 3.1 and 41.9 +/- 2.4 ng/ml/hr at the 1 and 10 mg/kg doses, respectively. Indomethacin inhibited this hydralazine-induced renin release by 100% at the 1 mg/kg dose and 36% at the 10 mg/kg dose even though the hypotensive effect of the drug was unaltered. Indomethacin (5 mg/kg) also suppressed urinary PGE2 excretion by 60% (p < 0.001). The beta-blocker, propranolol, was as effective as indomethacin in attenuating hydralazine-induced renin release. Additionally, propranolol blocked the tachycardia associated with hydralazine and slightly enhanced the hypotensive action of the drug. When indomethacin and propranolol were combined, no further inhibition of hydralazine-induced renin release was observed. Thus, renal PG's appear to be important as mediators of hydralazine-stimulated renin release but no hydralazine-induced vasodilatation.