Cgmp elevation does not mediate muscarinic agonist-induced negative inotropy in rat ventricular cardiomyocytes. Macdonell, Karen L., Glen F. Tibbits, and Jack Diamond. Faculty of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3. and School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada, V5A 1S6
APStracts 2:0284H, 1995.
Guanosine 3',5'-cyclic monophosphate (cGMP) has been suggested to be involved in the negative inotropic effects of muscarinic receptor agonists in [beta]-adrenergic receptor agonist-stimulated ventricular preparations. To test this hypothesis, changes in contractility induced by acetylcholine or carbachol, or the nitrovasodilator, sodium nitroprusside (SNP), in the presence of 1 nM isoproterenol were measured in electrically-stimulated rat ventricular cardiomyocytes. In parallel experiments, cardiomyocytes were treated with the same agonists and cGMP and adenosine 3',5'-cyclic monophosphate (cAMP) levels were estimated. After 2 min, isoproterenol increased the magnitude of cell shortening by 60% and accelerated contraction and relaxation rates. Carbachol (1 & 10 [mu]M) and acetylcholine (1 & 10 [mu]M) inhibited the positive inotropic effects of isoproterenol while SNP (10 & 100 [mu]M) had no inotropic effect. All three agents increased cGMP levels but had no effect on isoproterenol-stimulated cAMP levels. SNP caused the largest elevations in cGMP. These results suggest that the negative inotropic effects of muscarinic agonists observed in isoproterenol -stimulated rat ventricular cardiomyocytes are not mediated by alterations in cGMP and/or cAMP levels. 

Received 13 March 1995; accepted in final form 27 June 1995.
APS Manuscript Number H254-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.