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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Adenylate Cyclase Toxin, Adenylyl Cyclases, Adrenergic beta-Agonists, Animals, Arrhythmias, Cardiac, Carbachol, Colforsin, Cyclic AMP, GTP-Binding Proteins, Heart, In Vitro Techniques, Isoproterenol, Male, Myocardial Contraction, Myocardium, Norepinephrine, Pertussis Toxin, RNA, Messenger, Rats, Rats, Wistar, Receptors, Adrenergic, beta, Receptors, Muscarinic, Virulence Factors, Bordetella.
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Does chronic treatment with carbachol sensitize the myocardium to cAMP-induced arrhythmia? Context: The present study investigated biochemical and functional consequences of chronic activation of the inhibitory Gi alpha-coupled adenylyl cyclase pathway in the heart. Rats (220 to 260 g) were treated with 4-day infusions of the M-cholinoceptor agonist carbachol (9.6 mg/kg per day) or vehicle. An additional group that received the beta-adrenoceptor agonist isoprenaline (2.4 mg/kg per day) served as control. The main finding was that chronic infusion of carbachol led to a marked increase in isoprenaline- or forskolin-induced arrhythmia in electrically driven papillary muscles (in vitro). Compared with control, the potency of isoprenaline and forskolin to induce arrhythmia in cardiac preparations from carbachol-treated rats was increased 36- and 2.2-fold and the efficacy was increased 7.3- and 2.3-fold, respectively. The potency of carbachol to antagonize the isoprenaline- and forskolin-induced arrhythmia was decreased 30-fold. These changes were accompanied by a decrease in left ventricular M-cholinoceptor density by 15% (P < .05) and a decrease in pertussis toxin-sensitive G proteins (Gi alpha) by 26% (P < .05) without a decrease in the corresponding mRNAs. beta-Adrenoceptor density and basal and stimulated adenylyl cyclase activity remained unchanged. In contrast, isoprenaline infusion induced a decrease in arrhythmogenic potency of forskolin (P = NS), which was accompanied by a decrease in beta-adrenoceptor density, an increase in Gi alpha protein and mRNA levels, and a decrease in basal and stimulated adenylyl cyclase activity.
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Chronic parasympathetic activation sensitizes the myocardium to cAMP-induced arrhythmia. These changes may be due to quantitative alterations in functional Gi alpha. Final Decision: yes