Indomethacin inhibits responses to all vasoconstrictors in the rat mesenteric vascular bed: restoration of responses by prostaglandin E2.

Indomethacin added to the perfusing buffer inhibited pressor responses to noradrenaline, angiotensin II, arginine vasopressin, histamine, serotonin, calcium ions and potassium ions in the male rat mesenteric vascular bed. For every pressor agent the indomethacin concentration which inhibited response amplitude by 50% was about 7 microg/ml (2.1 X 10(-5) M). With every pressor agent, prostaglandin (PG) E2 could restore normal responsiveness in indomethacin-blocked preparations even while the indomethacin was still present in the buffer. The concentration of PGE2 required was proportional to the concentration of indomethacin. Preparations completely inhibited by indomethacin needed about 5ng/ml PGE2 for complete restoration of normal responses. Aspirin and mefenamic acid could also inhibit responses to all pressor agents tested but with these drugs only a partial restoration could be achieved by PGE2.