Mechanisms of the atrium-specific positive inotropic activities of quinidine- and atropine-like agents in rats.
This study investigated the mechanism of the positive inotropic effects of class 1 antiarrhythmic agents using electrically stimulated right atria (sinoatrial node excised), left atria and right ventricles of rats. Quinidine, disopyramide and procainamide produced concentration-dependent positive inotropic effects on right and left atria; effects on the right atria were greater than on left atria. At concentration producing positive inotropic effects on atria, the contractions of right ventricles were slightly increased by quinidine, unaffected by disopyramide and decreased by procainamide. The positive inotropic effects of quinidine were inhibited by propranolol, reserpine and mecamylamine but not by cocaine, hexamethonium and d-tubocurarine; propranolol also antagonized the positive inotropic effects of disopyramide and procainamide. Bupivacaine, which like quinidine blocks transient outward potassium current, slightly increased the contractions of right atria but not of left atria and ventricles. The atrium-specific positive inotropic effects of quinidine were mimicked by atropine, pirenzepine and dimethylphenylpiperazinium but not by nicotine, cytisine and butyrylcholine; the effects of atropine, dimethylphenylpiperazinium and pirenzepine were also blocked by propranolol. Quinidine increased the release of norepinephrine from atria but not from the ventricles; this release was greater from the right than from the left atria. It is concluded that quinidine- and atropine-like agents exert atrium-specific positive inotropic effects by blocking muscarinic receptors and permitting a dominance of acetylcholine effects via a release of norepinephrine from sympathetic nerve terminals.
Deng
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XF
Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
Mulay
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Chemtob
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Varma
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DR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology; D013268:Stimulation, Chemical
D000889:Anti-Arrhythmia Agents; D002395:Catecholamines; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D001285:Atropine; D011433:Propranolol; D004206:Disopyramide; D011802:Quinidine; D007545:Isoproterenol; D002045:Bupivacaine