Stress induced early renal injury by upregulating NADPH oxidase, hyperphosphorylation of PKCε is mitigated by endothelin receptor antagonist CPU0213

Abstract

Abstract: AIM: Stress likely contributes to oxidative stress initiating early renal insufficiency, that may relate to abnormal endothelin-1 (ET-1) -PKC(protein kinase C) εpathway.It is aimed to test if the endothelin receptor antagonist CPU0213 could reverse stress induced renal early lesion by suppressing abnormal ET and pPKCε. METHODS: Sprague-Dawley rats were subdivided into 3 groups:(1) normal, (2) isoproterenol (ISO) 1 mg/kg, s.c.for 10 days and (3) the ISO injected rats were intervened with CPU0213 20mg/kg, s.c., at day 6 -10.Biochemical measurements and expressions of ETAR (endothelin receptor A), NADPH oxidase p67^phox and PKCεwere conducted. RESULTS: Serum creatinine and 24 h urinary albumin were increased significantly (P < 0.01), compared with normal.The activities of GSHPx and SOD were decreased and the content of MDA was increased in the renal cortex associating with upregulated mRNA and protein of ETAR, PKC (, and NADPH oxidase p67^phox in ISO treated rats.CPU0213 was effective to reverse the renal function by suppressing the abnormalities. CONCLUSION: Activated ETAR, NADPH oxidase and pPKCεare assocaited with renal dysfunction in response to ISO.Endothelin receptor antagonist of CPU0213 is effective in reversing these changes.

Key words: endothelin receptor antagonist, NADPH oxidase-p67^phox, pPKCε, stress, renal injury

CLC Number:

R965.2

XU Jin, DAI De-zai, PENG Hong-jun, DAI Yin. Stress induced early renal injury by upregulating NADPH oxidase, hyperphosphorylation of PKCε is mitigated by endothelin receptor antagonist CPU0213[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(11): 1247-1252.

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