ROLE OF ENDOTHELIUM IN THE HUMAN UTERINE ARTERIES DURING NORMAL MENSTRUAL-CYCLE

1 The present experiments were designed to investigate the role of end othelium in the human uterine arteries during the normal menstrual cyc le. 2 Acetylcholine (ACh) produced a concentration-dependent relaxatio n 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 = 1 3; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruati on 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 (gro up III). Relaxation in response to A23187 in group II was not differen t 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 res ponse to ACh and the plasma E(2) was highly significant (gamma = 0.814 2, P<0.001) in 18 cases of groups I and II, but not in all 24 cases in cluding group III (gamma = 0.1183, NS). 4 Relaxations in response to A Ch in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh and A23187-induced relaxations were g reatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) an d partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was sig nificantly inhibited by methylene blue. 5 The A23187-induced relaxatio n was hardly affected by methylene blue or L-NOARG in group III, but w as partially inhibited by these agents in group II. The effect of indo methacin 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 hist ological changes in 14 cases out of 18 (groups I and II), but very sli ght intimal thickening was observed in 4 cases in group I. On the othe r hand, severe intimal thickening was observed in all 6 cases in group III. 7 These results indicate that, in human uterine artery strips, A Ch and A23187 cause endothelium-dependent relaxations, which are media ted 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 prod uction/release of EDRF/NO and/or of interaction between EDRF/NO and PG I(2) might play a role in the formation of intimal thickening in human uterine arteries.