TY - JOUR T1 - Effects of exogenous vasoconstrictors on coronary vascular resistance and prostacyclin production of the quiescent heart: the inhibitory effect of aspirin. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 44 LP - 49 VL - 248 IS - 1 AU - S L Lee AU - S Levitsky AU - H Feinberg Y1 - 1989/01/01 UR - http://jpet.aspetjournals.org/content/248/1/44.abstract N2 - The in situ heart is exposed to blood-borne vasoconstrictor agents (e.g., vasopressin) which, if unopposed, may cause radically increased coronary vascular resistance (CVR). Release of endogenous vasodilator, such as prostacyclin (PGI2), is a possible mitigating mechanism. We investigated the ability of the heart to maintain CVR within a narrow range when exposed to exogenous vasoconstrictors. The isolated rat heart was perfused at constant flow rate (5-6 ml/min) with oxygenated Krebs-Ringer bicarbonate solution (37 degrees C, pH 7.4), and was rendered quiescent by a local injection of lidocaine to the atrio-ventricular node. Changes of perfusion pressure, indicating changes of CVR, were monitored and the cardiac effluent was collected for analysis of 6-keto PGF1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2, respectively) by radioimmunoassay. Hearts were infused with four different vasoconstrictors (i.e., serotonin, vasopressin, angiotensin II and the thromboxane A2/PGH2 mimetic, U46619). There was a linear relationship between the dose-dependent increase in CVR and PGI2 production in serotonin, U46619 and vasopressin-infused quiescent heart. Vasoconstriction induced by angiotensin II was not dose-dependent and was unrelated to PGI2 production. Thus, PGI2 is produced in response to coronary vessel constriction, presumably to mitigate the constriction. No detectable thromboxane B2 was released by any of these vasoconstrictors. Partial inhibition (approximately 50%) of PGI2 production by aspirin (5.6 microM) treatment resulted in a paradoxically decreased vasoconstriction except at the lowest level of serotonin and vasopressin. Aspirin (1 mM) greatly reduced PGI2 production (approximately 90%) but the fall in CVR persisted.(ABSTRACT TRUNCATED AT 250 WORDS) ER -