Superoxide- and nitric oxide-derived species mediate endothelial dysfunction, endothelial glycocalyx disruption, and enhanced neutrophil adhesion in the post-ischemic guinea-pig heart

J Physiol Pharmacol. 2005 Jun;56(2):163-78.


The study was aimed at testing the hypothesis that a toxic product of the reaction between superoxide (O(2)(-)) and nitric oxide (NO) mediates, not only endothelial dysfunction, but also endothelium-glycocalyx disruption, and increased neutrophil (PMN) accumulation in the heart subjected to ischemia/reperfusion (IR) injury. Accordingly, we studied if scavengers of either O(2)(-) or NO, or a compound that was reported to attenuate cardiac production of peroxynitrite, would prevent endothelial injury and subsequent PNM adhesion in IR heart. Langendorff-perfused guinea-pig hearts were subjected to 30 min ischemia/35 min reperfusion, and infusion of PMN between 15 and 25 min of the reperfusion. Coronary flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures of endothelium-dependent and -independent vascular function, respectively. PMN adhesion and endothelium glycocalyx ultrastructure were assessed in histological preparations. IR impaired the ACh, but not SNP, response by approximately 60%, caused endothelium-glycocalyx disruption, and approximately nine-fold increase in PMN adhesion. These alterations were prevented by superoxide dismutase (150 U/ml), NO synthase inhibitor, L-NAME (10 microM), NO scavenger, oxyhemoglobin (25 microM), and NO donor, SNAP (1 microM), and were not affected by catalase (600 u/ml). The glycocalyx-protective effect of these interventions preceded their effect on PMN adhesion. The data imply that PMN adhesion in IR guinea-pig heart is a process secondary to functional and/or structural changes in coronary endothelium, and that a toxic product of the reaction between superoxide and NO mediates these endothelial changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Cell Adhesion
  • Coronary Circulation
  • Endothelium, Vascular / physiology*
  • Glycocalyx / metabolism*
  • Guinea Pigs
  • Myocardial Ischemia / physiopathology*
  • Neutrophils / physiology*
  • Nitric Oxide / metabolism*
  • Nitroprusside / pharmacology
  • Superoxides / metabolism*


  • Superoxides
  • Nitroprusside
  • Nitric Oxide
  • Acetylcholine