Modulation of angiotensin II coronary vasoconstriction by cardiac prostaglandin synthesis

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Abstract
To assess the ability of cardiac prostaglandin [PG] synthesis to attenuate the coronary vasoconstrictor effects of angiotensin[A]II, AII (0.05-0.20 .mu.g/kg per min i.v.) was infused in anesthetized dogs, coronary blood flow was measured by radioactive microspheres or electromagnetic flowmeter and plasma PG levels were measured by radioimmunoassay. Infusion of AII was associated with a rise in coronary sinus levels of PG E2 and PGF from undetectable levels to 80 .+-. 36 and 226 .+-. 43 pg/ml, respectively. Infusion of AII after indomethacin administration was associated with significantly (P < 0.05) lower levels of PGE2 (16 .+-. 4 pg/ml) and of PGF (46 .+-. 11 pg/ml) and with a 5-fold greater increase in coronary vascular resistance (54 .+-. 9% vs. 11 .+-. 5%; P < 0.01). Potentiation by indomethacin of AII-induced coronary vasoconstriction was limited to the left ventricular vasculature and occurred despite similar rises in mean arterial pressure and myocardial O2 consumption. Impaired left ventricular perfusion, manifested by widening of the arterial-coronary sinus O2 difference (15.8 .+-. 1.0 vs. 12.4 .+-. 1.2 ml/100 ml; P < 0.01) and a fall in cardiac output (2.1 .+-. 1.0 vs. 2.7 .+-. 0.3 l/min; P < 0.05) was observed only after indomethacin treatment. Cardiac PG synthesis is activated in the anesthetized dog during acute pathological elevations of circulating AII and PG synthesis attenuates the effect of the coronary vasoconstrictor on left ventricular myocardial blood flow.