PMID: 7744887Feb 1, 1995

Hypotensive effect of an M2-selective muscarinic antagonist in anaesthetized guinea-pigs

Journal of Autonomic Pharmacology
R E Howell, M P Kovalsky


1. In order to determine an involvement of muscarinic M2 receptors in the regulation of systemic arterial blood pressure, we investigated the cardiovascular effects of the M2-selective antagonist methoctramine and other agents in anaesthetized guinea-pigs. 2. Intravenous injection of methoctramine, atropine, pirenzepine (an M1-selective muscarinic antagonist) or 4-DAMP (an M3-selective muscarinic antagonist) each significantly increased heart rate in comparison to vehicle controls. 3. Methoctramine produced significant, dose-dependent decreases in mean arterial blood pressure, with an ED50 of 0.1 mg kg-1. Atropine decreased blood pressure only at high doses. Pirenzepine and 4-DAMP did not alter blood pressure, indicating that M1 or M3 receptor antagonism was not responsible for the cardiovascular effects of methoctramine. 4. The hypotensive effect of methoctramine was unaltered by indomethacin pretreatment, ruling out an alteration in arachidonic acid metabolism as the mechanism of action. 5. In contrast to methoctramine, mecamylamine (a nicotinic ganglionic receptor antagonist) greatly decreased heart rate and slightly decreased blood pressure, suggesting that ganglionic blockade was not the mechanism for the cardiovascular ef...Continue Reading


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