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

The effect of acetylcholine on isolated human uterine artery rings was investigated. Acetylcholine induced concentration and endothelium-dependent relaxation (pD2 = 7.29 +/- 0.03) of the precontracted arterial segments. The dissociation constant (KA) for acetylcholine was 1.35 (0.92-1.77) mumol/l. 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 pA2 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 M2 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 M3 subtype.