Key result
In isolated simian coronary arteries, acetylcholine-induced vasodilation is mediated by M3 receptors on endothelial cells, while vasoconstriction is mediated by M3 receptors on smooth muscle cells.
In isolated simian coronary arteries, both endothelium-dependent vasodilation and endothelium-independent vasoconstriction in response to acetylcholine are mediated by M3 muscarinic receptors.
Supports M3 receptor investigation in coronary vasomotion; leaves open human applicability.
Using the cannula insertion method, we investigated the vascular responses of isolated simian coronary artery to acetylcholine (ACh). When the preparation was partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose dependently in coronary artery with endothelium, but ACh and carbachol contracted the coronary artery after removal of the endothelium by 1 mg saponin. A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly. Both these responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol). The effects of three antagonists on the vasodilative responses to carbachol were also studied and almost the same results were observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)-induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not affect the action of isoproterenol. These data suggest that the vasodilation elicited by ACh is mediated by release of endothelium-derived relaxing factors (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the constriction is mediated by stimulation of M3 receptors on smooth muscle cells in isolated simian coronary arteries.
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Ren et al. (1993) studied Isolated simian coronary arteries. Acetylcholine (ACh) and carbachol vs. Various muscarinic antagonists (4-DAMP, AF-DX 116, pirenzepine) was evaluated on Vascular responses (vasodilation and vasoconstriction). In isolated simian coronary arteries, acetylcholine-induced vasodilation is mediated by M3 receptors on endothelial cells, while vasoconstriction is mediated by M3 receptors on smooth muscle cells.
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