Cholinergic modulation of enhanced vulnerability to ventricular fibrillation evoked by adrenergic stimulation in the isolated rat heart.
We investigated whether acetylcholine could antagonize the enhanced vulnerability to ventricular fibrillation evoked by adrenergic stimulation. Epinephrine, 5 X 10(-7)M, caused an 80% reduction in the ventricular fibrillation threshold and a 130% increase in the tissue level of cAMP. Acetylcholine 1 X 10(-7)M, 5 X 10(-7)M, and 1 X 10(-6)M, reduced the epinephrine-induced fall in the ventricular fibrillation threshold by 42%, 100%, and 94%, respectively. This antifibrillatory effect of acetylcholine could not be related to tissue levels of cGMP but rather was associated with reduced tissue levels of cAMP. These results demonstrate cholinergic modulation of the epinephrine-enhanced vulnerability to ventricular fibrillation and suggest that reduced accumulation of cAMP may underlie this effect.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009115:Muridae; D009206:Myocardium / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects*
D007473:Ion Channels; D011950:Receptors, Cholinergic; D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium; D004837:Epinephrine