Indomethacin and angiotensin II pressor responsiveness: importance of dietary sodium

Dietary sodium intake alters pressor responsiveness to angiotensin II (AII) as well as altering prostaglandin production. As a result, the effect of prostaglandin synthesis inhibition on the pressor responsiveness to AII was evaluated. Prostaglandin synthesis inhibition with meclofenamate (5 mg/kg) or indomethacin (5 mg/kg) significantly enhanced the pressor response for AII at infusion rates of 0.10, 0.30 and 1.0 microgram/kg per min (P less than 0.05) in rats previously on a low sodium intake but had no effect in rats previously on a high sodium intake. In low sodium intake rats, pretreatment with captopril (1 mg/kg) prevented the enhancing effect of indomethacin on angiotensin II pressor responsiveness. The pressor response for norepinephrine was unaltered by sodium intake or prostaglandin inhibition. These results suggest that prostaglandin synthetase inhibition may enhance the pressor response for angiotensin II in situations where endogenous angiotensin II levels are elevated (i.e. low sodium intake). In situations where angiotensin II levels are suppressed (i.e. captopril pretreatment or high salt intake), prostaglandin synthetase inhibitors have no effect on the pressor response to exogenous angiotensin II.