Beppu Masashi, Obayashi Satoshi, Aso Takeshi, Goto Moritaka, Azuma Hiroshi
Comprehensive Reproductive Medicine, Regulation of Internal Environment and Reproduction, Systemic Organ Regulation, Tokyo Medical and Dental University, Japan.
J Cardiovasc Pharmacol. 2002 Feb;39(2):192-200. doi: 10.1097/00005344-200202000-00005.
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.
本实验旨在研究绝经前后人类子宫动脉内皮细胞产生一氧化氮的能力、N（G）-单甲基-L-精氨酸（L-NMMA）和不对称N（G），N（G）-二甲基-L-精氨酸（ADMA）的浓度、血管壁内内皮素-1以及内膜增生程度（内膜/中膜比值）。根据基于基础环磷酸鸟苷水平的初步分类，16条动脉可分为I组和II组，每组各8条。I组核苷酸的净生成量显著高于II组。II组中L-NMMA与ADMA的浓度及内皮素-1含量显著更高。I组所有标本组织学均正常，而II组标本中观察到轻度至重度内膜增生。尽管在内膜/中膜比值、L-NMMA与ADMA及内皮素-1（每组各35个）方面可检测到相当大的个体差异，但这三个参数之间存在显著正相关，表明随着L-NMMA与ADMA及内皮素-1水平升高，内膜增生加剧。这些结果提示，内皮细胞中的内源性一氧化氮合酶抑制剂及血管壁内的内皮素-1是内膜增生的重要标志物。
