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Role of free radicals in vascular dysfunction induced by high tidal volume ventilation

2009; Springer Science+Business Media; Volume: 35; Issue: 6 Linguagem: Inglês

10.1007/s00134-009-1469-5

1432-1238

Leticia Martínez‐Caro, José A. Lorente, Judith Marín‐Corral, Carolina Sánchez‐Rodríguez, Alberto Sánchez‐Ferrer, Nicolás Nín, Antonio Ferruelo, Marta de Paula, Pilar Fernández-Segoviano, Esther Barreiro, Martin Dres,

Hydrogen's biological and therapeutic effects

To demonstrate that increased formation of reactive oxygen (ROS) and nitrogen species (RNS) is involved in VILI-induced vascular dysfunction. Male Sprague-Dawley anesthetized rats were ventilated for 60 min using low VT ventilation [VT 9 ml/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, n = 18], and high VT ventilation (VT 35 ml/kg, zero PEEP, n = 18). Arterial pressure and respiratory system mechanics were monitored. Blood samples for the determination of arterial blood gases and lactate concentration were drawn. Vascular rings from the thoracic aortae were mounted in organ baths for isometric tension recording. We studied endothelium-dependent relaxation in norepinephrine-precontracted rings (acetylcholine, 10 nM–10 μM) and contraction induced by norepinephrine (1 nM–10 μM) in resting vessels. Vascular rings were preincubated for 30 min with Zn–Mn–SOD (100 u/ml) or tempol (10−4 M) (extracellular and intracellular superoxide scavengers, respectively) or MnTMPyP (10−5 M) (a superoxide and peroxynitrite scavenger). The presence of superoxide and nitrotyrosine in aortic rings was evaluated by immunofluorescence. High VT ventilation induced hypotension, systemic acidosis, hypoxemia and hyperlactatemia, as well as impairment in acetylcholine and norepinephrine-induced responses in vitro. Responses to acetylcholine were improved by tempol (P = 0.004) and completely corrected (P < 0.001) by MnTMPyP. Responses to norepinephrine were also improved by treatment with tempol (P < 0.001) and MnTMPyP (P < 0.001). However, Zn–Mn–SOD did not improve acetylcholine- or norepinephrine-induced responses. Immunostaining for both superoxide and nitrotyrosine was increased in aortic rings from the high VT group. Our data support a role for intracellular ROS and peroxynitrite in the high VT ventilation-induced vascular dysfunction.