Effects of carvedilol in rats with induced chronic renal failure

Abstract

Hypertensive mechanisms are postulated to play,7 major role in the progressive glomeruloesclerosis (GS) after renal mass reduction. Previous studies have demonstrated differences in the progression to glomerulosclerosis with the use of different antihypertensive drugs. We analyzed whether the use of carvedilol (CVD) a new beta -adrenoceptor antagonist and vasodilator slows the progression of glomerulosclerosis in 5/6 nephrectomised (Nx) rats. Fifty-four adult Sprague-Dawley rats were distributed among five groups, four with 5/6 Nx, vehicle treated and CVD at 5, 10 and 20 mg/kg/day and sham (no renal ablation or drug treatment). Tail-cuff blood pressure, serum creatinine and urine protein concentration were measured. At the end of the experiment remnant kidney was removed for morphometric studies. Rats treated with 10 and 20 mg/kg/day of CVD showed controlled systemic blood pressure. Serum creatinine was similar in all treated groups with CVD, and half the levels observed in the vehicle-treated rats. The prevalence of glomerular lesions was closely associated with the degree of proteinuria. Eleven weeks after 5/6 Nx, vehicle-treated rats exhibited marked GS with 76% of affected glomeruli and creatinine retention. By contrast, renal injury was largely prevent in those rats treated with 10 and 20 mg/kg/day of CVD. Tuft enlargement oc curred in all groups but was more prominent in vehicle-treated group, 1.5 times higher than the group treated with 20 mg/kg/day of CVD. Although, these data demonstrate the importance of systemic blood pressure control in the renal protective efficacy of carvedilol, other less-known mechanisms of this drug must be investigated.