Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with prostacyclin and other prostanoids

Abstract

The effects of a recently synthesized, stable prostacyclin (PGI2) analog, 13,14-dehydro-PGI2 methyl ester, and authentic PGI2 and several other prostanoids on the coronary circulation were investigated in the intact dog by using a new technique to measure coronary sinus blood flow. The PGI2 analog, PGI2, and prostaglandin (PG) E2 and D2 each increased coronary sinus blood flow in a dose-related fashion when injected into the left coronary artery. The analog and PGE2 had similar vasodilator activity while PGI2 was slightly more potent. PGD2 was a moderately active coronary vasodilator whereas PGF2alpha was inactive. The coronary vasodilator effects of PGI2, its analog, PGE2, and PGD2 occurred at doses that had little effect on aortic pressure, left ventricular pressure and its first derivative, or on cardiac output and heart rate. The prostaglandin precursor arachidonic acid and the endoperoxide intermediate PGH2 both increased coronary sinus blood flow in a dose-dependent manner. The effects of arachidonic acid were inhibited by indomethacin. These data show that PGE2, PGI2, and a stable PGI2 analog are potent vasodilators in the canine coronary vascular bed and suggest that the vasodilator effects of arachidonic acid and PGH2 may be due to the formation of PGE2, PGD2, or PGI2 in the dog heart.