CGMP ELEVATION DOES NOT MEDIATE MUSCARINIC AGONIST-INDUCED NEGATIVE INOTROPY IN RAT VENTRICULAR CARDIOMYOCYTES

Guanosine 3',5'-cyclic monophosphate (cGMP) has been suggested to be i nvolved in the negative inotropic effects of muscarinic receptor agoni sts in beta-adrenergic receptor agonist-stimulated ventricular prepara tions. To test this hypothesis, changes in contractility induced by ac etylcholine or carbachol, or the nitrovasodilator sodium nitroprusside (SNP), in the presence of 1 nM isoproterenol were measured in electri cally stimulated rat ventricular cardiomyocytes. In parallel experimen ts, cardiomyocytes were treated with the same agonists, and cGMP and a denosine 3',5'-cyclic monophosphate (cAMP) levels were estimated. Afte r 2 min, isoproterenol increased the magnitude of cell shortening by 6 0% and accelerated contraction and relaxation rates. Carbachol (1 and 10 mu M) and acetylcholine (1 and 10 mu M) inhibited the positive inot ropic effects of isoproterenol, whereas SNP (10 and 100 mu M) had no i notropic effect. All three agents increased cGMP levels but had no eff ect on isoproterenol-stimulated cAMP levels. SNP caused the largest el evations in cGMP. These results suggest that the negative inotropic ef fects of muscarinic agonists observed in isoproterenol-stimulated rat ventricular cardiomyocytes are not mediated by alterations in cGMP and /or cAMP levels.