Central pressor effects induced by muscarinic receptor agonists: evidence for a predominant role of the M2 receptor subtype |
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| Authors: | A Pazos K H Wiederhold J M Palacios |
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| Institution: | 1. Research Laboratory of Experimental Neurochemistry, Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil;2. INFIQC-CONICET, Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina;3. Laboratory of Bioassays for Drug Research, Federal University of Pernambuco, Recife, PE, Brazil;4. Department of Pharmacy, Federal University of San Francisco Valley, Petrolina, PE, Brazil;5. Institute of Pharmaceutical Chemistry, University of Szeged, Hungary;6. Institute of Physics, University of São Paulo, São Paulo, SP, Brazil;7. Department of Parasitology, Adolf Lutz Institute, São Paulo, SP, Brazil;8. Research Center for Neglected Diseases, Guarulhos University, Guarulhos, SP, Brazil;9. Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil;1. Department of Food Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada;2. Ajinomoto Co. Ltd., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-8681, Japan |
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| Abstract: | The cardiovascular effects induced in the rat by several muscarinic receptor agonists were studied. All the agonists produced a clear decrease in heart rate. This decrease appeared to be peripherally mediated, because it was antagonized by methylscopolamine. The effects on blood pressure varied depending on the presence of anaesthesia, previous treatments and the type of agonists tested. When peripheral muscarinic activity was blocked by administration of methylscopolamine, a dose-dependent hypertension was obtained following the injection of oxotremorine, arecoline and aceclidine, by both intraperitoneal and intracerebroventricular routes. The muscarinic receptor agonist RS 86 produced a slight increase in blood pressure but the increase was weaker than those observed with the agonists cited above. On the other hand, the muscarinic receptor agonists pilocarpine, AF-30 and McN-A-343, considered as partially M1-selective compounds, did not produce any effect on blood pressure. Moreover, the hypertension induced by oxotremorine was completely blocked by intracerebroventricular administration of the non-subtype-selective muscarinic receptor antagonist scopolamine but was unaffected by the M1-selective antagonist pirenzepine. We propose that the central hypertensive response induced by muscarinic receptor agonists in the unanaesthetized rat is, at least partially, mediated through the stimulation of the so-called M2 muscarinic receptor subtype. |
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