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

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 PGF(1α). 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 the isolated bovine coronaries. The arachidonic acid 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 PGF(1α). 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 PGF(1α) like product, which is a potent coronary vasodilator.