1 The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2 Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E(2)) (follicular and luteal phases, E(2) = 131.9 +/- 15.9 pg ml(-1), n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E(2) = 19.8 +/- 2.9 pg mg(-1), n = 5; group II). During the follicular and luteal phases (E(2) = 181.1 +/- 9.0 pg ml(-1), n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P<0.05 and P<0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3 Correlation between the maximum response to ACh and the plasma E(2) was highly significant (gamma = 0.8142, P<0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4 Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was significantly inhibited by methylene blue. 5 The A23187-induced relaxation was hardly affected by methylene blue or L-NOARG in group III, but was partially inhibited by these agents in group II. The effect of indomethacin in inhibiting the A23187 induced-relaxation was most potent (58.9%) in group III and least (16.9%) in group I. 6 There were no histological changes in 14 cases out of 18 (groups I and II), but very slight intimal thickening was observed in 4 cases in group I. On the other hand, severe intimal thickening was observed in all 6 cases in group III. 7 These results indicate that, in human uterine artery strips, ACh and A23187 cause endothelium-dependent relaxations, which are mediated mainly through EDRF/NO in group I, mainly prostacyclin (PGI(2)) in group III, or both in group II, It is suggested that lack of the production/release of EDRF/NO and/or of interaction between EDRF/NO and PGI(2) might play a role in the formation of intimal thickening in human uterine arteries.
