Purpose: The balance between nitric oxide (NO) and endothelin-1 (ET-1 production is essential to vascular function in controlling organ perfusion, and an elevated ET-1 in the peritubular capillary network, following renal transplantation, can be associated with renal allograft rejection. The administration of a nitric oxide donor during the preischemic period has been shown to protect the kidneys against an ischemia-reperfusion injury, but the mechanism underlying this therapeutic benefit remains to be completely understood. Our hypothesis is that the early administration of the NO donor, sodium nitroprusside (SNP), may suppress ET-1, and thereby improve the renal function in an ischemia-reperfusion injury.
Methods: Sprague Dawley rats were subjected to 60 minutes of renal warm ischemia, followed by a contralateral nephrectomy. Renal biopsies were performed prior to ischemia and reperfusion, and at 1 and 48 hours after the reperfusion. The animals were divided into 4 groups: a sham group, without warm ischemia, an early SNP group (SNP given before schemia), a late SNP group (SNP given before reperfusion) and an ischemic control group. The ET-1 expression was assessed by a semiquantitative analysis by immunohistochemical staining with the ET-1 monoclonal antibody and Hematoxylin-Eosin stain. The serum creatinine was measured at 48 hours after the reperfusion.
Results: There were significant improvements in all parameters of the early SNP group compared with those in the late SNP and ischemic control groups, but there was no difference between the late SNP and ischemic control groups.
Conclusion: These data suggest that the early administration of SNP in renal ischemia-reperfusion improves the renal function by suppressing the expression of ET-1.
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