Changes in regional myocardial perfusion by muscarinic receptor subtypes in dogs

To determine the muscarinic receptor subtype (M1 or M2 or both) responsible for cholinergic coronary vasodilatation and alterations in the transmural distribution (endocardial to epicardial blood flow ratio) of coronary blood flow, systemic and coronary haemodynamic indices and regional myocardial blood flow (radioactive microspheres) were measured in anaesthetised dogs. Submaximal vasodilative doses of the mixed muscarinic agonist acetylcholine were given by intracoronary infusion to avoid peripheral haemodynamic effects. Acetylcholine produced significant increases in myocardial perfusion and selectively redistributed flow to the subendocardium (increased endocardial to epicardial blood flow ratio). Pirenzepine (160 nmol X kg-1 iv), a selective M1 antagonist, produced no change in endocardial to epicardial blood flow ratio or myocardial blood flow but blocked the increase in endocardial to epicardial blood flow ratio and attenuated the transmural increase in myocardial perfusion during acetylcholine infusion. 4-Diphenylacetoxy-N-methylpiperidine methyl bromide (4-DAMP) (17 nmol X kg-1 iv), a selective M2 antagonist, also attenuated the transmural increase in myocardial blood flow but had little effect on the increase in endocardial to epicardial blood flow ratio produced by acetylcholine. These results support the hypothesis that M1 muscarinic coronary receptors are responsible for the redistribution of blood flow to the subendocardium (increased endocardial to epicardial blood flow ratio) during cholinergic coronary vasodilatation, whereas both M1 and M2 receptors are involved in increasing myocardial perfusion.