Modulation of beta adrenergic responsiveness by arachidonic acid metabolites in isolated bovine coronary arteries.
The present study was designed to determine whether interference with endogenous arachidonic acid metabolism or exogenously administered cyclooxygenase and lipoxygenase products affects the relaxation of bovine coronary artery in response to isoproterenol. Rings of bovine coronary artery were suspended for isometric tension recordings in organ chambers filled with Krebs-Ringer bicarbonate solution (37 degrees C) gassed with 95% O2-5% CO2 (pH 7.4). In depolarized coronary artery rings (35 mM KCI) isoproterenol induced a dose-dependent relaxation, which was significantly augmented by the cyclooxygenase inhibitor indomethacin and depressed by arachidonic acid. The mixed lipoxygenase/cyclooxygenase inhibitor phenidone or the lipoxygenase products leukotriene D4 and C4 did not affect beta adrenergic responsiveness. Phenidone antagonized the facilitatory action of indomethacin. Exogenous arachidonic acid in the presence of indomethacin and phenidone depressed the relaxation induced by isoproterenol. Prostacyclin and prostaglandin E2 reduced beta adrenergic responsiveness, which was not affected by indomethacin. The data suggest that arachidonic acid depresses beta adrenergic responsiveness in the bovine coronary artery via cyclooxygenase and some noncyclooxygenase, nonlipoxygenase metabolites. Lipoxygenase products, other than leukotrienes D and C, may have a facilitatory action.
Rubanyi
G M
GM
Paul
R J
RJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011720:Pyrazoles; D011943:Receptors, Adrenergic, beta; D013189:SRS-A; D016718:Arachidonic Acid; D011189:Potassium Chloride; D011464:Epoprostenol; C015429:phenidone; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin