Impaired endothelium-dependent relaxation after coronary reperfusion injury: Evidence for G-protein dysfunction

P. R B Evora, P. J. Pearson, Hartzell V Schaff

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G- protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetylcholine was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-L-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, was unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium- dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury leads to G-protein dysfunction in the endothelium.

Original languageEnglish (US)
Pages (from-to)1550-1556
Number of pages7
JournalAnnals of Thoracic Surgery
Volume57
Issue number6
StatePublished - 1994

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Myocardial Reperfusion
Reperfusion Injury
GTP-Binding Proteins
Endothelium
Endothelium-Dependent Relaxing Factors
Reperfusion
Oxides
Myocardial Ischemia
Coronary Vessels
Sodium Fluoride
Pertussis Toxin
Calcimycin
Type C Phospholipases
Cardiopulmonary Bypass
Constriction
Adenosine Diphosphate
Acetylcholine
Canidae
Nitric Oxide
Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Impaired endothelium-dependent relaxation after coronary reperfusion injury : Evidence for G-protein dysfunction. / Evora, P. R B; Pearson, P. J.; Schaff, Hartzell V.

In: Annals of Thoracic Surgery, Vol. 57, No. 6, 1994, p. 1550-1556.

Research output: Contribution to journalArticle

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