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We have studied the involvement of nitric oxide (NO) and prostacyclin (PGI2) as well as muscarinic m2 and m3 receptors in the coronary vasodilatation induced by acetylcholine in the isolated hearts of guinea pig and mouse perfused according to the Langendorff method. In the guinea pig heart, a coronary vasodilator response to acetylcholine was profoundly decreased by the NO-synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME, 10(-4) M), while in the mouse heart this response was blocked by the cyclooxygenase inhibitor indomethacin (5 x 10(-6) M). In both cases, the muscarinic m3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 3 x 10(-8) M) blocked the acetylcholine-induced vasodilator response, while the muscarinic m2 antagonist methoctramine (3 x 10(-7) M) had no effect. It was concluded that the vasodilator effect of acetylcholine depends on NO in the coronary circulation of guinea pig and on PGI2 in the coronary circulation of mouse. In both cases, the coronary vasodilation induced by acetylcholine is mediated by muscarinic m3 receptors.
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