The hypothesis that elevation of intracellular
guanosine 3':5' cyclic monophosphate (
cyclic GMP) concentrations may increase electrical stability of the myocardium was examined by determination of
ventricular fibrillation thresholds (VFT) on isolated perfused hearts of the rat. Hearts were paced to circumvent any complicating effects of
bradycardia. Using this system,
carbachol produced a concentration-related reduction in VFT. The reduction in VFT produced by
carbachol was not significantly modified by a high concentration of
atenolol (10(-5)M), indicating that the increased vulnerability to
ventricular fibrillation was not an indirect consequence of
catecholamine release from intramyocardial stores.
Atropine (10(-6)M) blocked the
carbachol-induced reduction in VFT. At the concentrations of
carbachol used to reduce VFT, myocardial
cyclic GMP concentrations were also elevated. The dibutyryl analogue of
cyclic GMP (10(-4)M) mimicked the effect of
carbachol in reducing VFT.
Carbachol potentiated the
adrenaline (3 X 10(-7)M)-induced reduction in VFT.