The inhibition of prostaglandin synthetase in vivo by nonsteroidal anti-inflammatory agents.

The effects of two nonsteroidal anti-inflammatory compounds, fenclorac and indomethacin, on arachidonate and prostaglandins (PG) E1- and E2-induced vasodepressor responses were determined in the spontaneously hypertensive male rat. A 0.4 to 2 mg/kg intravenous dose of fenclorac blocked the arachidonate-induced vasodepressor response and had no effect on PGE1- and E2-induced hypotension. Similar responses were observed after indomethacin. These results were indicative of in vivo inhibition of PG synthetase by fenclorac and indomethacin. Administration of propranolol did not alter the arachidonate or PG responses; regitine reduced the arachidonate and PG response, suggesting that alpha-adrengergic receptors in vascular smooth muscle may play a role in the prostaglandin-induced hypotension.