1J1430 Involvement of NO synthase(NOS), arginase and dimethylarginine dimethylaminohydrolase(DDAH) in the intimal hyperplasia in perimenopausal human uterine arteries

Fifty two human uterine arteries were obtained from 52 perimenopausal patients undergoing total hysterectomy under the informed consent for the present study. The specimens were assessed histologically to determine the intima：media ratio (I/M, %) as an index of intimal hyperplasia. Nineteen specimens were found to be histologically normal (I/M=16.1±0.8%), whereas remaining 33 specimens were categorized as hyperplasic (I/M=34. ±1.5%). Intimal hyperplasia was accompanied by the decreased basal and stimulated cyclic GMP productions without change in NOS activity, increased L-NMMA and ADMA concentrations as endogenous NOS inhibitors, decreased DDAH activity, and increased arginase activity which shares L-arginine as a common substrate with NOS. these findings suggest that de decreased cyclic GMP production as a marker of NO production is possibly due to the accumulation of endogenous NOS inhibitors and increased arginase activity, which in turn, causes intimal hyperplasia in human uterine arteries and that the accumulation of Nos inhibitors is closely related to the decreased DDAH activity which is a metabolizing enzyme of NOS inhibitors. The increased arginase activity may plasy a role for the vascular remodeling pathway in a manner of cyclic GMP independent mechanism.