Increased cytochrome P4502E1 expression and altered hydroxyeicosatetraenoic acid formation mediate diabetic vascular dysfunction: rescue by guanylyl-cyclase activation.

ABSTRACT:

Objective

We investigated the mechanisms underlying vascular endothelial and contractile dysfunction in diabetes as well as the effect of HMR1766, a novel nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC).

Research design and methods

Two weeks after induction of diabetes by streptozotocin, Wistar rats received either placebo or HMR1766 (10 mg/kg twice daily) for another 2 weeks; thereafter, vascular function was assessed.

Results

Endothelial function and contractile responses were significantly impaired, while vascular superoxide formation was increased in the aortae from diabetic versus healthy control rats. Using RNA microarrays, cytochrome P4502E1 (CYP2E1) was identified as the highest upregulated gene in diabetic aorta. CYP2E1 protein was s

SUBMITTER: Schafer A 

PROVIDER: S-EPMC2911073 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature