Blockade of coronary reactions to arachidonic acid by glyceryl trinitrate and tranylcypromine.
Isolated perfused hearts of rats or guinea pigs reacted to bolus doses of arachidonic acid (AA) with a coronary constriction followed by a protracted vasodilatation phase. Glyceryl trinitrate (GTN; 55-95 microM) produced coronary dilatation during which the AA-induced constriction remained unaltered, or even enhanced. After 'acute tolerance' developed by sustained GTN infusion, the constrictor phase of AA was inhibited while the vasodilatation continued unaltered or slightly enhanced. Nitroprusside (Np; 5-56 microM) determined a coronary vasodilatation that persisted throughout its administration and appeared to be associated with an inhibition of the AA-induced coronary constriction. While withdrawal of Np resulted in an immediate recovery of coronary flow levels and of the reactions to AA, the blockade of AA-coronary constriction continued after GTN withdrawal. Tranylcypromine (TRC) infusion did not alter the basal coronary flow, but it produced a specific inhibition of the AA-induced coronary vasodilatation. We postulated that the blockade of the coronary constriction exerted during GTN acute tolerance would result from an inhibition of the synthesis of a constrictor metabolite (thromboxane-like substance?) formed in the coronaries through the cyclooxygenase metabolic pathway of AA.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis; D014191:Tranylcypromine / Q000494:pharmacology*; D014664:Vasodilation
D001095:Arachidonic Acids; D009599:Nitroprusside; D016718:Arachidonic Acid; D014191:Tranylcypromine; D013928:Thromboxane A2; D011464:Epoprostenol; D005996:Nitroglycerin