Possible involvement of facilitated polyol pathway in augmentation of intimal hyperplasia in rabbits with alloxan-induced hyperglycemia.

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.
AuthorsMoritaka Goto, Yukinao Yamauchi, Emi Kurosaki, Hiroshi Azuma
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 41 Issue 2 Pg. 265-75 (Feb 2003) ISSN: 0160-2446 [Print] United States
PMID12548088 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • L-Iditol 2-Dehydrogenase
  • Animals
  • Carotid Arteries (enzymology, pathology)
  • Diabetes Mellitus, Experimental (enzymology, pathology)
  • Endothelium, Vascular (enzymology, pathology)
  • Hyperplasia (enzymology, pathology)
  • L-Iditol 2-Dehydrogenase (metabolism)
  • Male
  • Rabbits
  • Signal Transduction (physiology)
  • Tunica Intima (enzymology, pathology)

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