CARVEDILOL PROTECTS AGAINST GLOMERULOSCLEROSIS IN RAT REMNANT KIDNEY WITHOUT GENERAL CHANGES IN ANTIOXIDANT ENZYME STATUS - A COMPARATIVE-STUDY OF 2 BETA-BLOCKING DRUGS, CARVEDILOL AND PROPRANOLOL

Nephron loss leads to increased production of reactive oxygen intermed iates. We measured the effect of carvedilol, a beta-blocking drug with radical scavenging properties, on renal function, glomerulosclerosis, antioxidant enzyme status and in vivo hydrogen peroxide (H2O2) produc tion in rats with chronic renal failure caused by 5/6 nephrectomy (rem nant kidney) and compared results to data obtained with propranolol, a beta-blocking drug without scavenging characteristics. Carvedilol and propranolol were administered during 11 weeks following reduction of nephron number. Kidneys were examined using enzymatic and histological techniques. Both carvedilol and propranolol decreased systolic blood pressure. Compared to propranolol, carvedilol offered some additional beneficial effects on renal function, particularly with regard to glom erulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-h ydroxynonenal concentration in cortex homogenates, was decreased in ca rvedilol-treated rats only. Superior beneficial effect of carvedilol t reatment is not linked to a significant up-regulation of the activitie s of the remnant kidney antioxidant enzymes (catalase, glutathione per oxidase and superoxide dismutase) or to a decreased in vivo H2O2 produ ction.