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CARDIOVASCULAR

Vascular Dysfunction of Venous Bypass Conduits Is Mediated by Reactive Oxygen Species in Diabetes: Role of Endothelin-1

Clinical and Experimental Therapeutics Program, University of Georgia College of Pharmacy (A.E., A.K.H., J.H.), Vascular Biology Center (A.E., A.T., M.P.A.), Departments of Surgery (A.R., E.R., B.W., M.P.A.) and Pharmacology and Toxicology (R.W.C.), Medical College of Georgia, Augusta, Georgia; and University of Tromsø Institute of Pharmacy, Tromsø, Norway (J.S.J., C.S.)

Diabetes is associated with increased risk for complications following coronary bypass grafting (CABG) surgery. Augmented superoxide production plays an important role in diabetic complications by causing vascular dysfunction. The potent vasoconstrictor endothelin-1 (ET-1) is also elevated in diabetes and following CABG; however, the effect of ET-1 on generation and/or vascular dysfunction in bypass conduits remain unknown. Accordingly, this study investigated basal and ET-1-stimulated production in bypass conduits and determined the effect of on conduit reactivity. Saphenous vein specimens were obtained from nondiabetic (n = 24) and diabetic (n = 24) patients undergoing CABG. Dihydroethidium staining and NAD(P)H oxidase activity assays (5380 ± 940 versus 16,362 ± 2550 relative light units/µg) demonstrated increased basal levels in the diabetes group (p < 0.05). Plasma ET-1 levels were associated with elevated basal levels, and treatment of conduits with exogenous ET-1 further increased production and augmented vasoconstriction. Furthermore, vascular relaxation was impaired in the diabetic group (75 versus 40%), which was restored by scavenger superoxide dismutase. These findings suggest that ET-1 causes bypass conduits dysfunction via stimulation of production in diabetes. Novel therapies that attenuate generation in bypass conduits may improve acute and late outcome of CABG in diabetic patients.

Address correspondence to: Dr. Adviye Ergul, Medical College of Georgia, Clinical Pharmacy CJ-1020, 1120 15th Street, Augusta, GA 30912. E-mail: aergul{at}mail.mcg.edu

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