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

• Autorzy: Kurzelewski M. , Czarnowska E. , Baresewicz A.
• Języki publikacji: EN

Abstrakty

EN

The study was aimed at testing the hypothesis that a toxic product of the reaction between superoxide (O2-) 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 O2- 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 µM), NO scavenger, oxyhemoglobin (25 µM), and NO donor, SNAP (1 µM), 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.

Słowa kluczowe

EN

superoxide; endothelium glycocalyx; nitric oxide; guinea pig; oxygen free radical; heart; neutrophil adhesion; endothelial dysfunction

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2005
• Tom: 56
• Numer: 2
• Opis fizyczny: p.163-178,fig.,ref.

Twórcy

autor

Kurzelewski M.

• Medical Centre of Postgraduate Education, Marymoncka 99, 01-813 Warsaw, Poland

autor

Czarnowska E.

autor

Baresewicz A.