Comparative effects of arachidonic acid, bisenoic prostaglandins, and an endoperoxide analog on the canine pulmonary vascular bed

Abstract

The effects of bolus injections of the prostaglandin [PG] precursor, arachidonic acid and PGD2, PGF2.alpha., PGE2 and the PGH2 analog ((15S)-hydroxyl-9.alpha.,11.alpha.(epoxymethano)prosta-5Z-dienoic acid) were compared on pulmonary circulation in the intact spontaneously breathing pentobarbital-anesthetized dog. Arachidonic acid increased pulmonary arterial pressure, decreased aortic pressure and increased cardiac output when injected into the superior vena cava or right atrium. PGE2, like arachidonic acid, increased pulmonary arterial pressure and cardiac output and decreased aortic pressure, whereas PGF2.alpha. and PGD2 increased pulmonary arterial pressure but did not affect cardiac output or aortic pressure when injected into the superior vena cava or right atrium. The PGH2 analog increased pulmonary arterial pressure and to a lesser extent, aortic pressure, without affecting cardiac output. None of these substances changed left atrial or right atrial pressure. The cardiopulmonary effects of arachidonic acid were blocked by indomethacin, whereas the rise in pulmonary arterial pressure in response to the bisenoic prostaglandins and the analog were enhanced by the cyclooxygenase inhibitor. The increase in pulmonary vascular resistance in response to arachidonic acid may be due to conversion of the precursor into vasoactive intermediates and products such as bisenoic prostaglandins, whereas the decrease in systemic vascular resistance is probably due to formation of PGE2 and other peripheral vasodilator substances.