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.