The effect of cholinergic agonists on coronary flow rate and oxygen consumption in isolated perfused rat heart.

The metabolic and circulatory consequences of activation of the muscarinic receptor(s) were investigated by local administration of acetylcholine and its three analogues (bethanechol, carbachol and methacholine) into beating and KCl-arrested perfused rat hearts. Acetylcholine and the three other choline esters caused vasoconstriction in both types of preparations and this vasoconstriction was accompanied by a decrease in oxygen consumption. In most cases the dose-response curves were biphasic and changes in coronary flow paralleled those in oxygen consumption. Both phenomena were abolished by administration of atropine and either removal of calcium or infusion of verapamil but were unaffected by addition of the adrenergic alpha-blocker, prazosin, and the adrenergic beta-blocker, propranolol. Infusions of low concentrations of the cholinergic agonists were accompanied by increases in the myocardial phosphorylation state ratio [( ATP]free/[ADP]free[Pi]) which correlated with the simultaneous decreases in oxygen consumption and coronary flow. It is suggested that muscarinic receptors responsible for vasoconstriction in perfused rat heart are located not only on coronary vessels but also on the cardiac muscle cells. Activation of the former receptors induces vasoconstriction by direct action on the vascular smooth muscle while activation of the latter receptors induces vasoconstriction indirectly by decreasing cardiac work and increasing the myocardial [ATP]free/[ADP]free[Pi] ratio. The results also show that stimulation of muscarinic receptor(s) and the consequent metabolic and vasoregulatory responses are coupled to calcium movements.