renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of vili the role of the peroxynitrite-parp pathway肾低灌注和endothelium-dependent受损血管舒张的动物模型vili peroxynitrite-parp通路的作用.pdfVIP

Vaschetto et al. Critical Care 2010, 14:R45 /content/14/2/R45 R E S E A R C H Open Access Research Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway 2,4 4,5 4,5 1 Rosanna Vaschetto*1,2,3,4, Jan W Kuiper , René JP Musters , Etto C Eringa , Francesco Della Corte , Kanneganti Murthy6, AB Johan Groeneveld3,4 and Frans B Plötz2,4 Abstract Introduction: Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite. Methods: Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clear