Endothelium-dependent relaxation in response to acetylcholine in the human uterine artery

Abstract

The effect of acetylcholine on isolated human uterine artery rings was investigated. Acetylcholine induced concentration and endothelium-dependent relaxation (pD 2 = 7.29 ± 0.03) of the precontracted arterial segments. The dissociation constant ( K A) for acetylcholine was 1.35 (0.92–1.77) μmol/1. The occupancy-response relationship was non-linear. Half-maximal response to acetylcholine was obtained with 5.25% receptor occupancy. Muscarinic receptor antagonists: atropine, pirenzepine, methoctramine, p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) and 4-diphenyl-acetoxy- N-methyl-piperidine (4-DAMP) competitively antagonized the response to acetylcholine. The constrained pA 2 values were 9.32 ± 0.03, 7.13 ± 0.01, 6.26 ± 0.01, 8.17 ± 0.01 and 9.13 ± 0.02, respectively. A selective muscarinic M 2 receptor antagonist, gallamine, had no effect on acetylcholine-induced relaxation. It is concluded that in human uterine arteries acetylcholine induces endothelium-dependent relaxation and acts as a full agonist. We suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of the isolated human uterine artery are predominantly of the M 3 subtype.