Endogenous nitric oxide synthase inhibitors in endothelial cells, endothelin-1 within the vessel wall, and intimal hyperplasia in perimenopausal human uterine arteries.
The present experiments were designed to investigate the ability to produce nitric oxide, concentrations of N(G)-monomethyl-L-arginine (L-NMMA), and asymmetric N(G), N(G)-dimethyl-L-arginine (ADMA) in endothelial cells, endothelin-1 within the vessel wall, and the degree of intimal hyperplasia (intima/media ratio) in perimenopausal human uterine arteries. According to the tentative classification based on basal cyclic GMP levels, 16 arteries could be grouped into groups I and II consisting of eight each. Net production of the nucleotide was significantly higher in group I than that in group II. Concentration of L-NMMA plus ADMA and endothelin-1 content were significantly higher in group II. All specimens from group I were histologically normal, whereas mild to severe intimal hyperplasia was observed in group II specimens. Although considerable individual variations were detectable in the intima/media ratio, L-NMMA plus ADMA and endothelin-1 (n = 35 each), there were significant and positive correlations between three parameters, indicating that intimal hyperplasia became greater as L-NMMA plus ADMA and endothelin-1 were increased. These results suggest that endogenous nitric oxide synthase inhibitors in endothelial cells and endothelin-1 within the vessel wall are important markers of intimal hyperplasia.
Beppu
Masashi
M
Comprehensive Reproductive Medicine, Regulation of Internal Environment and Reproduction, Systemic Organ Regulation, Tokyo Medical and Dental University, Japan.
Obayashi
Satoshi
S
Aso
Takeshi
T
Goto
Moritaka
M
Azuma
Hiroshi
H
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D002979:Climacteric; D006152:Cyclic GMP / Q000096:biosynthesis; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014599:Uterus / Q000098:blood supply*; D019323:omega-N-Methylarginine / Q000378:metabolism
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP