Alterations of arachidonic acid metabolism modulate adenosine relaxation in isolated coronary arteries.
The possible modulation of adenosine-induced relaxation by endogenous prostaglandins was studied in isolated porcine, bovine and canine coronary arteries. Artery rings were mounted for isometric tension recording in organ bath filled with Krebs-Ringer-bicarbonate solution (37 degrees C). Increasing concentrations (10(-6)-10(-4) M) of adenosine relaxed contractions induced by 35 mM KCl. The cyclo-oxygenase inhibitor indomethacin (5 X 10(-6) M) significantly augmented the relaxations in response to adenosine in coronary arteries isolated from all three species. In the porcine coronary artery (which was most sensitive to exogenous adenosine) the mixed lipoxygenase/cyclo-oxygenase inhibitor phenidone augmented, while exogenous arachidonic acid (3 X 10(-5) M) or a decrease in bath O2-level from 95 to 20% depressed adenosine-induced relaxations. Indomethacin completely prevented the inhibitory effect of decreasing bath O2, but only partially antagonized the suppression caused by arachidonic acid. The data demonstrate that arachidonic acid and its cyclo-oxygenase metabolites modulate (depress) adenosine responsiveness in isolated coronary arteries.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D013552:Swine
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; D011189:Potassium Chloride; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C015429:phenidone; D000241:Adenosine; D007213:Indomethacin