Hemodynamic Change and Hypoxic Inducible Factor-1alpha and Inducible Nitric Oxide Synthase Expression of Ipsilateral Kidney during Acute Stage of Ureteropelvic Junction Obstruction in Adult Rat

Lee, Sang Don; Lee, Chang Hun; Choi, Eun Ho

Abstract

Purpose: This study aimed to evaluate the expression of inducible nitric oxide synthase (iNOS) and hypoxic inducible factor-1alpha (HIF-1alpha) and the hemodynamic changes in the renal medulla and cortex, during the acute stages of an unilateral ureteropelvic junction obstruction (UPJO) in adult rats.
Materials and Methods
Kidney specimens were aseptically removed from 35 Sprague- Dawley 8 week old adult rats, weighing 250-300gm, from a sham groups, 0, 6, 12 and 24 hours, and an experimental groups (UPJO 6, 12 and 24 hours). The renal blood flow of the ipsilateral kidney was measured at the left main renal artery using a laser flowmeter. The expressions of HIF-1alpha and iNOS, for the hypoxic changes to the ipsilateral kidney, were evaluated by immunohistochemical staining and a Western blot assay.
Results
There were no significant differences in the blood flows of the main renal arteries immediately prior to the operations in any of the groups. However, there was a significant difference in the blood flows between the before an operation, and just before a nephrectomy, after a UPJO, in all the experimental groups. There was a significant decrease in the renal blood flow in the experimental group compared to those in the sham group. The expressions of iNOS and HIF-1alpha in the ipsilateral kidney, as shown by the immunohistochemical staining, were markedly increased in relation to the time of the obstruction, especially in medulla, and those shown by the Western blot assays were increased in the total renal tissue, medulla and cortex, compared to the sham groups.
Conclusions
A decreased renal blood flow in the ipsilateral kidney, during the acute stages of the unilateral UPJO, generally enhanced the expressions of the iNOS and HIF-1alpha in the medulla. This study suggests that hypoxia of the ipsilateral kidney, after an UPJO, induces HIF-1alpha, and then enhances the production of NO by the activation of iNOS, which finally results in renal ischemic damage.