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 (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) mu mol/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 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.