Open AccessPossible Involvement of Facilitated Polyol Pathway in Augmentation of Intimal Hyperplasia in Rabbits with Alloxan-induced Hyperglycemia
Author(s) -
Minoru Goto,
Yukinao Yamauchi,
Emi Kurosaki,
Hiroshi Azuma
Publication year - 2003
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200302000-00016
Subject(s) - polyol pathway , medicine , intimal hyperplasia , endocrinology , hyperplasia , aldose reductase , alloxan , polyol , arginine , nitric oxide , saline , endogeny , chemistry , diabetes mellitus , biochemistry , smooth muscle , amino acid , organic chemistry , polyurethane
Present experiments were designed to investigate whether the facilitated polyol pathway is involved in the augmentation of intimal hyperplasia with hyperglycemia. Twelve weeks after a single bolus intravenous injection of alloxan (100 mg/kg) or saline, rabbits underwent a unilateral endothelial denudation of the carotid artery. Intimal hyperplasia was evident 4 weeks after denudation and significantly augmented in hyperglycemic animals treated with alloxan. This effect was accompanied by the enhanced accumulation of endogenous NOS inhibitors (N(G)-monomethyl-l-arginine [l-NMMA] and asymmetric, N(G),N(G)-dimethyl-l-arginine [ADMA]) in regenerated endothelial cells, impairment of NO production and release, and enhanced accumulation of endothelin-1 (ET-1) within the vessel wall. Sorbitol levels in aortic endothelial cells and within the smooth muscle layer were significantly increased with hyperglycemia. All these changes associated with hyperglycemia were significantly reduced in animals treated with the selective aldose reductase inhibitor fidarestat (3 mg/kg/d). These findings suggest that the facilitated polyol pathway possibly plays an important role for the augmentation of intimal hyperplasia caused by the hyperglycemic state.