Arachidonic acid (AA, 10(-8)-5 X 10(-6) M) induced dose-dependent relaxations of canine coronary arterial rings precontracted with dinoprost that were significantly greater (P less than .001) if the endothelium was intact. Cyclooxygenase inhibition with indomethacin displaced the dose-response curve to AA to the right but did not prevent the relaxant effects of the fatty acid. SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes, also attenuated the response to AA although the combination of SKF-525A and indomethacin prevented any relaxant effect. Induction of cytochrome P-450-dependent enzymes in the coronary artery with 3-methylcholanthrene and beta-naphthoflavone given in vivo (40 mg/kg/day for 3 days) or depletion of these enzymes with cobalt chloride (24 mg/kg/day for 2 days) resulted in an enhancement or diminution, respectively, of AA-induced endothelial-dependent relaxations. These results implicate a cytochrome P-450-dependent mixed function oxidase in the endothelial-dependent relaxations to AA in the canine coronary artery. Precontraction of coronary arteries with U46619 in contrast to dinoprost failed to display endothelial-dependent relaxations to AA, whereas the responses to bradykinin and acetylcholine were also partially attenuated. Pharmacologic manipulations of AA metabolism via cyclooxygenase and cytochrome P-450-dependent monooxygenases indicate that the endothelial-dependent relaxations induced by bradykinin are partially dependent upon metabolites of AA, whereas the relaxations produced by acetylcholine are independent of AA metabolites, suggesting that a number of potential relaxing factors may be released from the endothelium
Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: Contribution of a cytochrome P-450-dependent pathway
PINTO, Aldo;
1987
Abstract
Arachidonic acid (AA, 10(-8)-5 X 10(-6) M) induced dose-dependent relaxations of canine coronary arterial rings precontracted with dinoprost that were significantly greater (P less than .001) if the endothelium was intact. Cyclooxygenase inhibition with indomethacin displaced the dose-response curve to AA to the right but did not prevent the relaxant effects of the fatty acid. SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes, also attenuated the response to AA although the combination of SKF-525A and indomethacin prevented any relaxant effect. Induction of cytochrome P-450-dependent enzymes in the coronary artery with 3-methylcholanthrene and beta-naphthoflavone given in vivo (40 mg/kg/day for 3 days) or depletion of these enzymes with cobalt chloride (24 mg/kg/day for 2 days) resulted in an enhancement or diminution, respectively, of AA-induced endothelial-dependent relaxations. These results implicate a cytochrome P-450-dependent mixed function oxidase in the endothelial-dependent relaxations to AA in the canine coronary artery. Precontraction of coronary arteries with U46619 in contrast to dinoprost failed to display endothelial-dependent relaxations to AA, whereas the responses to bradykinin and acetylcholine were also partially attenuated. Pharmacologic manipulations of AA metabolism via cyclooxygenase and cytochrome P-450-dependent monooxygenases indicate that the endothelial-dependent relaxations induced by bradykinin are partially dependent upon metabolites of AA, whereas the relaxations produced by acetylcholine are independent of AA metabolites, suggesting that a number of potential relaxing factors may be released from the endotheliumI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
