Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta

N. Jaiswal, G. Lambrecht, E. Mutschler, R. Tacke, Kafait Malik

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Studies were performed in the rabbit aortic rings, precontracted with norepinephrine, to determine the subtype(s) of muscarinic receptors involved in endothelium-dependent relaxation and contraction in the absence of endothelium elicited by cholinergic stimuli. Acetylcholine (ACh) and arecaidine propargyl ester (APE), a M2 and M3 agonist, produced a dose-dependent relaxation and contraction in endothelium-intact and endothelium-denuded rabbit aortic rings, respectively. Both of these responses were blocked by the muscarinic receptor antagonist atropine. M1 selective agonist McN-A-343 {4-[N-(3-chlorophenyl)carbamoyloxy[-2-butinyltrimethylammonium chloride} did not produce any effect on the tone of precontracted aortic rings. ACh- and APE-induced relaxation in aortic rings with intact endothelium was selectively blocked by M3 receptor antagonists hexahydrosila-difenidol and p-fluoro-hexahydro-sila-difenidol (pA2 of 7.84 and 7.18) but not by M1 antagonist pirenzepine or M2 receptor antagonists AF-DX 116 {11-(2-[(diethylamino)methyl]-1-piperidinyl]acetyl)-5, 11-dihydro-6H-pyrido-[2,3-b][1,4]-benzo-diazepin-6one} and methoctramine. ACh- and APE-induced contraction was inhibited by M2 receptor antagonists AF-DX 116 and methoctramine (pA2 of 7.11 and 6.71) but not by pirenzepine, hexahydro-sila-difenidol or p-fluoro-hexahydro-sila-difenidol. ACh- and APE-induced relaxation or contraction were not altered by nicotinic receptor antagonist hexamethonium or cyclooxygenase inhibitor indomethacin. These data suggest that relaxation elicited by cholinergic stimuli in endothelium-intact aortic rings is mediated via release of endothelium-derived relaxing factor consequent to activation of M3 receptors located on endothelial cells, whereas the contraction in aortic rings denuded of their endothelium is mediated via stimulation of M2 receptors located on smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)842-850
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number3
StatePublished - Jan 1 1991

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Muscarinic Receptors
Endothelium
Blood Vessels
Aorta
Pharmacology
Rabbits
Acetylcholine
Pirenzepine
Cholinergic Agents
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Nicotinic Antagonists
Endothelium-Dependent Relaxing Factors
Hexamethonium
Muscarinic Antagonists
Cyclooxygenase Inhibitors
Nicotinic Receptors
Atropine
Indomethacin
Smooth Muscle Myocytes
Chlorides

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta. / Jaiswal, N.; Lambrecht, G.; Mutschler, E.; Tacke, R.; Malik, Kafait.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 258, No. 3, 01.01.1991, p. 842-850.

Research output: Contribution to journalArticle

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