Nitric oxide synthase does not participate in the negative inotropic effect of acetylcholine in the frog heart. M[acute]ery, Pierre-Fran[cedilla]cois, Leif Hove-Madsen, Jean-Michel Chesnais, H. Criss Hartzell, and Rodolphe Fischmeister. Laboratoire de Cardiologie Cellulaire et Mol[acute]eculaire, INSERM CJF 92-11, Universit[acute]e de Paris-Sud, Facult[acute]e de Pharmacie, F-92296 Ch[circumflex]atenay-Malabry, France; and the Heart Cell Laboratory, Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322
APStracts 2:0397H, 1995.
In the heart, the parasympathetic neurotransmitter acetylcholine (ACh) reduces the force of contraction. Although the effect of ACh can be partly explained by an inhibition of adenylyl cyclase, there is evidence that some of the effects of ACh may also be mediated via stimulation of nitric oxide synthase (NOS), and production of cyclic GMP (cGMP). NOS inhibitors can prevent the negative chronotropic effect of ACh on spontaneously beating cardiomyocytes, and suppress the inhibition of the L-type calcium current (ICa) by ACh in sino -atrial myocytes. This pathway may be relevant not only to the chronotropic effect of ACh, but also to its inotropic effect, since ACh, NO, and cGMP regulate the force of contraction and ICa in the cardiac ventricle. Here we report the effects of L-arginine (L-Arg), the substrate of NOS, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro -L-arginine (L-NNA), two NOS inhibitors, on the muscarinic effects in the cardiac ventricle. We found that L-Arg, L-NMMA and L-NNA have no effect on the muscarinic inhibition of ICa in isolated frog myocytes. Besides, these compounds have no significant effects on the basal ICa, and on the [beta]-adrenergic stimulation of ICa. L-Arg and its analogs did not change the negative inotropic effect of ACh in frog ventricular fibers. The basal active tension or the positive inotropic effect of isoprenaline, a [beta]-adrenergic agonist, were also unaffected. We conclude that NOS is not involved in the muscarinic inhibition of ICa in isolated frog ventricular myocytes, nor in the negative inotropic effect of ACh in the frog ventricle. 

Received 7 April 1995; accepted in final form 30 August 1995.
APS Manuscript Number H343-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.