Alteration of p66shc is associated with endothelial dysfunction in the abdominal aortic coarctation of rats

To examine the role of p66shc in endothelial dysfunction, we investigated the endothelium- dependent relaxation, protein expression and superoxide production in abdominal aortic coarctation rats. Endothelium- dependent relaxation to acetylcholine was impaired only in the aortic segments above the aortic coarctation ( 35.0 +/- 7.1% vs. 86.6 +/- 6.0% for sham control at 1 lM Ach). The aortic segments exposed to increased blood pressure showed a decreased phosphorylation of endothelial nitric oxide synthase, an increased phosphorylation of p66shc, and an increased superoxide production. Angiotensin II elicited a signi. cantly increased phosphorylation of p66shc in the endothelial cells. Taken together, these. ndings suggest that the increased phosphorylation of p66shc is one of the important mediators in the impaired endothelium- dependent relaxation of aortic coarctation rats. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.