1J1354 Involvement of decreased DDAH activity, increased arginase activity, and accumulated endogenous NOS inhibitors in the initiation and/or progression of intimal hyperplasia following endothelial denudation

Intimal hyperplasia started to occur 1week after the endothelial denudation of the rabbit carotid artery and was accompanied by the significantly increased arginase and NOS activities, significantly decreased DDAH activity, significantly decreased NO production, accumulation of endogenous NOS inhibitors and decreased L-arginine content in regenerated endothelial cells. Since L-arginine is a common substrate for arginase and NOS, the greatly increased arginase activity may lead to the decreased NO production although NOS activity itself was increased. Furthermore, accumulation of endogenous NOS inhibitors and decreased L-arginine content possibly relate to the decreased NO production. There was a negative correlationship between NO production and magnitude of intimal hyperplasia, that is, the magnitude of intimal hyperplasia became greater as NO production was decreased. In addition, the magnitude of intimal hyperplasia became greater as concentrations of endogenous NOS inhibitors were increased in regenerated endothelial cells, which had probably been brought about by the decreased DDAH activity as a degradating enzyme of endogenous NOS inhibitors. All these changes may closely relate to the initiation and/or progression of intimal hyperplasia following endothelial denudation.