Does indomethacin antagonize the effects of peptides and other agents on the coronary circulation of rabbit isolated hearts.

The coronary vasodilator effects of substance P, bradykinin, eledoisin, adenosine, and nitroglycerin have been tested in rabbit isolated hearts perfused with physiological medium. It has been found that substance P is the most potent vasodilator and that the peptides are 10-100 times as active as adenosine and nitroglycerin. The effect of bradykinin is reduced by 50% in the presence of indomethacin (2.8-5 X 10(-6) M) while the actions of the other vasodilator are not influenced. At such concentrations, indomethacin is inactive on its own and blocks the effects of small and intermediate doses of arachidonic acid, the prostaglandin precursor. It suggested that edogenous prostaglandins do not play any major role in mediating the coronary vasodilation produced by several peptide and nonpeptide agents, but may account for about 50% of the effect of bradykinin.