The roles of inducible NO synthase and reactive oxygen species on lung injury induced by renal ischemia/reperfusion injury in the isolated perfused rat lung

Abstract

Background: Acute kidney injury (AKI) is a severe disorder with high incidence of morbidity and mortality word wild. Acute lung injury (ALI) is one of the proposed but controversial complications of AKI. The aim of this study was to determine the effect of kidney injury on pulmonary capillary permeability and hypoxic response of pulmonary vascular bed in rat. Method: We investigated the effects of 1 hr bilateral or 2 hr unilateral renal ischemia/reperfusion as well as bilateral or unilateral nephrectomy followed by 24 hr recovery, on pulmonary capillary filtration coefficient, weight gain and water retention in the isolated ventilated perfused rat lung. Pulmonary vascular resistance was measured during hypoxic gas ventilation. We also examined the effect of aminoguanidine, a selective iNOS inhibitor and antioxidant Trolox, a water soluble vitamin E analog to find out the role of NO and ROS at above conditions. Results: Both bilateral renal ischemia/reperfusion and bilateral nephrectomy increased pulmonary capillary filtration coefficient, lung weight gain and water retention. Unilateral ischemia/reperfusion or unilateral nephrectomy had no effect on pulmonary capillary permeability. Trolox but not aminoguanidine prevented increase in pulmonary capillary permeability in bilateral ischemia/reperfusion and bilateral nephrectomy. Conclusion: This study was the first to indicate the role of reactive oxygen species in ALI induced by AKI in the isolated rat lung. However, more studies are needed to clarify the effects of long term kidney injury on lung injury.