Dynamics of vagal chronotropic effects during blockade of different types of muscarinic cholinergic receptors

Abstract

Different changes in vagal chronotropic effects were observed in cats under blockade of various types of muscarinic cholinergic receptors. Burst stimulation of the vagus nerve caused synchronization of the vagal and cardiac rhythms, which was potentiated by M a and M 3 receptor antagonists and suppressed by the M 2 blocker gallamine. The components of the vagal chronotropic effect showed different sensitivity to selective M-cholinolytics.Key Words: muscarini cholinergic receptors; vagal chronotropic effect Heterogenous population of muscarinic cholinergic receptors includes at least 5 subtypes which are distinguished by their structure, location, and functional properties [7]. In the myocardium, M2receptors are the predominant type of receptors. They mediate the inhibitory effects of the vagus nerve (VN) stimulation. However, there is evidence that other types of cholinergic receptors are also implicated in the regulation of cardiac activity. For instance in rats and guinea pigs, the intracardial neurons contain RNAs encoding four types of muscarinic receptors (M1-M 4) [9]. Receptors of different types may play different functional roles. For instance, in dogs MI receptor blockade significantly weakened the vagal chronotropic effect (VCE), but did not affect the vagal influence on the myocardial conductivity and contractility [5,12].These findings can be used in the analysis of VCE mechanisms. Along with the inhibitory tonic component, the chronotropic effect contains a synchronizing component that controls cardiac rhythm under conditions of VN stimulation [13]. These components are probably associated with different muscarinic receptors. In this study we checked up this hypothesis. MATERIALS AND METHODSExperiments were carried out on 27 cats weighing 3-4 kg anesthetized with intraperitoneal Chloralose-NemDepartment Physiolo9y, Kuban Medical Academy, Krasnodar butai mixture (75:15 mg/kg) and 'artificially ventilated. The peripheral end of the right VN was stimulated with short 40 Hz trains of 3, 6, or 9 rectangular pulses of 0.2 msec duration and 5-6 thresholds' intensity. Amplified ECG was recorded by a unipolar probe inserted through the femoral vein into the right atrium. The following selective M-receptor antagonists were used: pirenzepine (M1), gallamine (M2), and 4-diphenylacetoxy-N-(2-chlorethyl)-piperidine (4-DAMP. M3) [6]. The drugs (0.002-0. 2 mg/kg ) were infused intravenously. The data were analyzed statistically by the method of direct differences [ 1 ].