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.