Characterization of a novel metabolic pathway of arachidonate in coronary arteries which generates a potent endogenous coronary vasodilator

Abstract

Bovine coronary artery strips were incubated with [1-14C]arachidonic acid and the chemical properties of the various prostaglandins (PG) formed were studied. Arachidonate was converted to two major prostaglandin products, PGE2 and a novel prostaglandin having chemical (i.e. base hydrolysis and borohydride reduction) and chromatographic properties identical with 6-keto-PGF1alpha. This final compound was inactive on coronary artery strips. The endoperoxide intermediates, PGG2 or PGH2, previously shown to induce coronary relaxation, were not released into the medium from isolated bovine coronaries. The arachidonic acid-induced dilation may have been due to an intracellular action of PGH2 (or PGG2) or to the action of another, yet unidentified, labile intermediate formed in the enzymatic conversion of endoperoxides to 6-keto PGF1alpha. When PGH2 was incubated with bovine coronary microsomes, the PGH2 was completely metabolized (i.e. loss of rabbit aorta contraction) but a compound was generated which was a much more potent coronary relaxant. We suggest that this major novel metabolic pathway of arachidonate generates a substance, intermediate between PGH2 and the final 6-keto PGF1alpha-like product, which is a potent coronary vasodilator.