title: Role of endothelium in the human uterine arteries during normal menstrual cycle.
abstract: 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 (E2) (follicular and luteal phases, E2 = 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 (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 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 E2 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(PGI2) 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 PGI2 might play a role in the formation of intimal thickening in human uterine arteries.
authors.affiliation: Department of Medicinal Chemistry, Institute for Medical and Dental Engineering, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Azuma
authors.forename: S
authors.initials: S
authors.lastname: Obayashi
authors.forename: H
authors.initials: H
authors.lastname: Hamasaki
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.forename: T
authors.initials: T
authors.lastname: Aso
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000098:blood supply* / Q000502:physiology
chemical_list: D014280:Triglycerides; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D004958:Estradiol; D001120:Arginine; D002784:Cholesterol; D000109:Acetylcholine