The effect of a nitric oxide donor on endogenous endothelin-1 expression in renal ischemia/reperfusion injury.

The balance between nitric oxide (NO) and endothelin-1 (ET-1) production is essential to the vascular function that controls organ perfusion. Elevated ET-1 levels in the peritubular capillary network following renal transplantation may be associated with renal allograft rejection. Administration of a nitric oxide donor during the preischemic period has been shown to protect kidney against ischemia-reperfusion injury, but the mechanism underlying this therapeutic benefit remains incompletely understood. We hypothesized that early administration of the NO donor sodium nitroprusside (SNP) may suppress ET-1, thereby improving renal function in an ischemia/reperfusion injury. Sprague-Dawley rats were subjected to 60 minutes of renal warm ischemia and contralateral nephrectomy. Renal biopsies were performed prior to ischemia and reperfusion, and at 1 hour and 48 hours after reperfusion. The animals were divided into four groups: sham group without warm ischemia; early SNP group (SNP given before ischemia); late SNP group (SNP given before reperfusion); and ischemic control. ET-1 expression was assessed by semiquantitative analysis with immunohistochemical stain using ET-1 monoclonal antibody and hematoxylin-eosin staining. Serum creatinine was measured at 48 hours after reperfusion. There were significant improvements in all parameters of the early compared with the late SNP group and the ischemic control, but there was no difference between the late SNP group and the ischemic control. These data suggest that early administration of SNP in renal ischemia-reperfusion improves renal function by suppressing ET-1 expression.