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

100%

Kurzelewski M., Czarnowska E., Baresewicz A.

Journal of Physiology and Pharmacology

2005

tom 56

nr 2

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.

Nitric oxide synthase inhibition and elevated endothelin increase oxygen consumption but do not affect glucose and palmitate oxidation in the isolated rat heart

100%

Kurzelewski M., Duda M., Stanley W. C., Baresewicz A.

Journal of Physiology and Pharmacology

2004

tom 55

nr 1,1

Evidence indicates that nitric oxide (NO) suppresses myocardial oxygen consumption (MVO2) and regulates myocardial substrate oxidation, however data from in vivo and isolated heart preparations are conflicting. In addition, cardiac endothelin (ET-1) release has been shown to increase with inhibition of NO synthase (NOS), however the effects of ET-1 on myocardial energetics is not clear. We employed the isolated rat heart model to assess the role of NO and ET-1 on myocardial function and metabolism. Oxidation of glucose and FFA was measured using [U-14C]glucose and [9,10-3H]palmitate. NOS inhibition with NG-methyl-L-arginine acetate salt (L-NMMA, 50 µM), resulted in an increase in MVO2 at a given rate of myocardial external workload, and no change in myocardial glucose or FFA oxidation. ET-1 (25 pM), which caused coronary vasoconstriction similar to that produced by L-NMMA, also increased MVO2 without an effect on cardiac workload, or substrate oxidation, suggesting a role for ET-I in the regulation of myocardial energetics. We assessed also the effect of ETA/ETB receptor blockade (tezosentan; 5 nM) on MVO2 and glucose and FFA oxidation and observed no effect, suggesting that basal ET-1 production does not play a role in regulating MVO2 or substrate selection. In conclusion, inhibition of NOS or the addition of ET-1 resulted in an increase in MVO2, but did not affect glucose or FFA oxidation.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Baresewicz A.

2 Kurzelewski M.

1 Czarnowska E.

1 Duda M.

1 Stanley W. C.

1 2005

1 2004

Wyniki wyszukiwania

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

Nitric oxide synthase inhibition and elevated endothelin increase oxygen consumption but do not affect glucose and palmitate oxidation in the isolated rat heart