Indomethacin attenuates the hypotensive action of hydralazine

To determine whether indomethacin affects the vasodilator action of hydralazine in man, we studied nine healthy human subjects in a crossover, double-blind, randomized trial. Subjects received either oral indomethacin (200 mg) or placebo, after which they received two 0.15 mg/kg doses of intravenous hydralazine given 30 minutes apart. During the placebo phase there was a prompt hypotensive response after the first dose of hydralazine, with concomitant increases in heart rate, renal blood flow, and plasma norepinephrine and epinephrine levels but no consistent changes in forearm blood flow or vascular resistance. In contrast, the hypotensive response in the indomethacin phase occurred only after the second dose of hydralazine, and the magnitude of change in blood pressure was less than that in the placebo phase. The effects of hydralazine on heart rate, renal blood flow, limb blood flow, and plasma catecholamine levels were not affected by indomethacin. These results suggest that prostaglandins do play a role in the medication of the vasodilator effects of hydralazine, because its hypotensive effect was attenuated by indomethacin. However, this interaction must occur in vascular beds other than the limb or renal circulations, where no effect of indomethacin was observed.