Effects of sodium and calcium concentrations on the potentiation by indomethacin of the responses of rabbit mesenteric and coeliac arteries to vasoconstrictor agonists.
The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5-hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 microM) The potentiation was similar whether indomethacin was added 1 h before or during the response to the agonist. The agonists that were more potentiated by indomethacin were also more dependent on the Ca2+ concentration in the medium, for their contractile action. Prostaglandin E2 in low concentrations (micromolar) did not affect the resting tone but relaxed the agonist-contracted arteries both in normal and in Ca2+-free medium. No prostaglandin E (PGE)-like substances were detected in the perfusate of arteries contracted by angiotensin. Reduction of the external Na+ concentration to 80 mM resulted in potentiation of the responses to agonists (angiotensin and adrenaline), but not to K+, and in this Na+-deficient medium potentiation by indomethacin was greatly reduced. These results suggest that potentiation by indomethacin of the arteries' responses to vasoactive substances may result from that drug's inhibitory action on sodium influx and consequent increase in calcium entry through receptor-operated channels.
D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002445:Celiac Artery / Q000187:drug effects; D002645:Chickens; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000809:Angiotensins; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D012964:Sodium; D002118:Calcium; D007213:Indomethacin