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The Antiarrhythmic Effect and Possible Ionic Mechanisms of Pilocarpine on Animal Models

Bio-Pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State, Key Laboratory, Harbin, PR China

Han-ping Qi, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Ying Liu, MD

Nutrition and Food Hygiene Harbin Medical University, Harbin, PR China

Wei Chen, MD

Bio-Pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State, Key Laboratory, Harbin, PR China

Jing Xie, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Zhen-yu Pan, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Hong-mei Han, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Li-peng Chen, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Dan-lu Li, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Li-yan Wang, MD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Hong-li Sun, MD, PhD

Department of Pharmacology Harbin Medical University, Harbin, PR China

Yan Liu, MD, PhD

Department of Pharmacology Harbin Medical University, Harbin, PR China, liuyangy2000{at}yahoo.com.cn

This study was designed to evaluate the effects of pilocarpine and explore the underlying ionic mechanism, using both aconitine-induced rat and ouabain-induced guinea pig arrhythmia models. Confocal microscopy was used to measure intracellular free-calcium concentrations ([Ca²⁺]_i) in isolated myocytes. The current data showed that pilocarpine significantly delayed onset of arrhythmias, decreased the time course of ventricular tachycardia and fibrillation, reduced arrhythmia score, and increased the survival time of arrhythmic rats and guinea pigs. [Ca²⁺]_i overload induced by aconitine or ouabain was reduced in isolated myocytes pretreated with pilocarpine. Moreover, M₃-muscarinic acetylcholine receptor (mAChR) antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) partially abolished the beneficial effects of pilocarpine. These data suggest that pilocarpine produced antiarrhythmic actions on arrhythmic rat and guinea pig models induced by aconitine or ouabain via stimulating the cardiac M₃-mAChR. The mechanism may be related to the improvement of Ca²⁺ handling.

Key Words: animal models • arrhythmias • Ca2+ • M3mAChR • pilocarpine

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 14, No. 3, 242-247 (2009)
DOI: 10.1177/1074248409339308


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