Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats

We have investigated the influence of a novel angiotensin II type 1 recepto r antagonist, candesartan cilexetil, on the oxidative state of renal tissue and renal function in 5/6 nephrectomized rats, and compared its effects wi th those of an angiotensin-converting enzyme inhibitor, enalapril. Candesar tan cilexetil (1 and 5 mg/kg per day), enalapril (5 mg/kg per day) and vehi cle were orally administered once daily for 16 weeks after 5/6 nephrectomy. There was a marked degree of proteinuria evident prior to treatment, an av erage of 5.69 mg/mg creatinine in the nephrectomized rats, vs 1 to 2 mg/mg creatinine in the control group matched for species and body weight. Inhibi tion of development of proteinuria by candesartan cilexetil was dose depend ent. Enalapril also significantly blunted the rise in urinary protein. Malo ndialdehyde content in the homogenate from the renal cortex increased signi ficantly in the nephrectomized rats compared to control animals. This eleva tion of malondialdehyde content was unaffected by administration of either candesartan cilexetil or enalapril. Antioxidative enzyme (glutathione perox idase, superoxide dismutase, and catalase) activities in the renal tissue w ere not affected by any active treatment. Elevation of lipid peroxide in re mnant renal tissue suggests that oxidative stress may contribute to the pro gression of renal injury in the nephrectomized rats. Neither candesartan ci lexetil nor enalapril affected antioxidant defenses in renal tissue in neph rectomized rats, indicating that mechanisms other than alteration in oxidat ive stress are involved in the renoprotective effects of candesartan cilexe til and enalapril.