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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Endothelin-1
Blood Vessels
Reactive Oxygen Species
Diabetic Angiopathies
NADPH Oxidase
Saphenous Vein
Vasoconstrictor Agents
Vasoconstriction
Superoxides
Superoxide Dismutase
Staining and Labeling
Light
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes : Role of endothelin-1. / Ergul, Adviye; Johansen, Jeanette Schultz; Strømhaug, Catherine; Harris, Alex K.; Hutchinson, Jimmie; Tawfik, Amany; Rahimi, Ali; Rhim, Edward; Wells, Bryan; Caldwell, William W.; Anstadt, Mark P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 313, No. 1, 01.04.2005, p. 70-77.

Research output: Contribution to journalArticle

Ergul, Adviye ; Johansen, Jeanette Schultz ; Strømhaug, Catherine ; Harris, Alex K. ; Hutchinson, Jimmie ; Tawfik, Amany ; Rahimi, Ali ; Rhim, Edward ; Wells, Bryan ; Caldwell, William W. ; Anstadt, Mark P. / Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes : Role of endothelin-1. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 313, No. 1. pp. 70-77.
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