PROSTACYCLIN (PGI2) INDUCES CORONARY VASODILATATION IN ANESTHETIZED DOGS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 12  (12) , 720-730
Abstract
Prostacyclin (PG[prostaglandin]I2), the predominant metabolite of arachidonic acid in isolated hearts, relaxes strips of bovine coronary artery and is a potent vasodilator in isolated perfused hearts. The actions of PGI2 on coronary blood flow in open chest dogs anesthetized with chloralose were examined. An electromagnetic flow probe was fitted to the left circumflex artery and phasic coronary flow, mean coronary flow (a measure of coronary volume flow over 4 s intervals), and coronary vascular resistance were recorded wtih aortic pressure and heart rate. I.v. infusion of PGI2 (0.05-1.0 .mu.g/kg per min) reduced coronary vascular resistance and aortic pressure according to dose, but had only small effects on phasic coronary flow or mean coronary flow. Tachycardia and bradycardia occurred during PGI2 infusion but 6-oxo-prostaglandin F1.alpha. (infused at 10 .mu.g/kg per min), the stable degradation product of PGI2, had no cardiovascular effects. The coronary vasodilator effects of PGI2 were clear when it was injected into the left circumflex artery via a fine catheter distal to the flow probe. PGI2 (0.05-0.5 .mu.g) increased phasic coronary flow and mean coronary flow up to 3-fold and reduced coronary vascular resistance without affecting aortic pressure or heart rate, although higher doses had systemic effects. PGE1 (0.1-0.5 .mu.g), which also dilated the coronary vessels, had a longer lasting effect and was 1-4 times more potent than PGI2. PGE2 (0.5-4 .mu.g) was less potent than PGI2. In 4 dogs PGI2 (20-500 .mu.g) applied epicardially to the left ventricle caused marked and prolonged coronary vasodilatation. Epicardial application of PGI2 (10-25 .mu.g) to the right ventricle increased coronary sinus O2 content with minimal changes in blood pressure. The endoperoxide PGH2 was a coronary vasodilator of similar potency to PGI2, but its epoxymethano-analog U46619 is a vasoconstrictor. Inhibition of cyclo-oxygenase with indomethacin (5 mg/kg i.v.) or sodium meclofenamate (2 mg/kg i.v.) potentiated the coronary dilator effects of PGI2 given i.v. or into the coronary artery. Cyclo-oxygenase inhibition did not alter the hypotensive effects and increased the coronary vasodilator potency of PGI2 relative to PGE2. The sensitivity of the coronary vascular bed to PGI2 was enhanced when endogenous biosynthesis of PG-like substances was inhibited. Although the importance of arachidonic acid metabolites in the coronary circulation still requires validation in vivo, it is clear that PGI2, and not PGE2, is the PG most likely to be involve.