Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: Role of endothelin-1

Adviye Ergul, Jeanette Schultz Johansen, Catherine Strømhaug, Alex K. Harris, Jimmie Hutchinson, Amany Tawfik, Ali Rahimi, Edward Rhim, Bryan Wells, William W. Caldwell, Mark P. Anstadt

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Abstract

Diabetes is associated with increased risk for complications following coronary bypass grafting (CABG) surgery. Augmented superoxide ( .O2.-) 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 .O2.- generation and/or vascular dysfunction in bypass conduits remain unknown. Accordingly, this study investigated basal and ET-1-stimulated .O2.- production in bypass conduits and determined the effect of .O2.- 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 .O 2.- levels in the diabetes group (p < 0.05). Plasma ET-1 levels were associated with elevated basal .O2 .- levels, and treatment of conduits with exogenous ET-1 further increased .O2.- production and augmented vasoconstriction. Furthermore, vascular relaxation was impaired in the diabetic group (75 versus 40%), which was restored by .O2 .- scavenger superoxide dismutase. These findings suggest that ET-1 causes bypass conduits dysfunction via stimulation of .O 2.- production in diabetes. Novel therapies that attenuate .O2.- generation in bypass conduits may improve acute and late outcome of CABG in diabetic patients.

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume313
Issue number1
DOIs
StatePublished - Apr 1 2005

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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