Prostacyclin release following endoperoxide analogue infusion in the intact dog.
We examined the systemic and coronary hemodynamic responses after infusion of an endoperoxide analogue U 46,619 in anesthetized dogs and related the hemodynamic effects to the release of thromboxane A2 (TXA2) and prostacyclin (PGI2). Immediately after U 46,619 infusion, increases in mean arterial and left ventricular end-diastolic pressures (LVEDP) occurred, whereas coronary and aortic blood flows were unchanged. Calculated vascular resistances in the systemic and coronary vascular beds increased significantly. At 3-5 min after infusion, mean arterial pressure and LVEDP spontaneously decreased and vascular resistances also declined, whereas coronary and aortic blood flows were unchanged. Simultaneously measured plasma TXB2 and 6-keto-PGF1 alpha (stable hydrolysis metabolites of TXA2 and PGI2, respectively) increased in the femoral and coronary arterial blood samples in conjunction with the vasoconstrictor effects. At 3-5 min, plasma 6-keto-PGF1 alpha concentrations showed a further increase, whereas TXB2 concentrations slightly decreased, suggesting release of PGI2 as a possible mechanism of vasodilation. To examine this possibility, nine dogs were treated with cyclooxygenase inhibitors (aspirin or indomethacin) and given U 46,619. In these animals neither vasoconstrictor nor vasodilator effects were observed. Plasma TXB2 and 6-keto-PGF1 alpha concentrations also did not increase after U 46,619. These data show that the vasoconstrictor and platelet aggregatory agent U 46,619 results in PGI2 release in the dog. Release of PGI2 may be a protective and autoregulatory mechanism in the canine systemic and coronary vascular beds.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood
D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol