Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney / 대한신장학회지

ABSTRACT

PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats. METHODS: Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry. RESULTS: Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed. CONCLUSION: The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.