COMPARISON BETWEEN CARVEDILOL AND CAPTOPRIL IN RATS WITH PARTIAL ABLATION-INDUCED CHRONIC-RENAL-FAILURE

1 The effect of the novel beta-adrenoceptor antagonist and vasodilator , carvedilol (SK&F 105517, approximately 70 mg kg-1 daily in the food) , and captopril (approximately 38 mg kg-1 daily in the drinking fluid) on the progression of chronic renal failure in rats was studied. 2 Si x weeks following partial renal ablation, the urinary protein excretio n of the carvediol- (60 +/- 21 mg day-1) and captopril-treated (35 +/- 9 mg day-1) animals was less than 50% that of control rats (133 +/- 2 7 mg d-1). 3 Serum creatinine (Scr) and urea nitrogen (SUN) concentrat ions of the carvedilol-(Scr, 0.63 +/- 0.09 mg dl-1; SUN, 11.3 +/- 1.2 mg dl-1) and captopril-treated (Scr, 0.82 +/- 0.05 mg dl-1; SUN, 14.1 +/- 1.5 mg dl-1) animals were also significantly (P < 0.05) lower than that observed in control animals (Scr, 1.4 +/- 0.3 mg dl-1; SUN, 19.2 +/- 3.9 mg dl-1), indicating that glomerular filtration rate was impr oved by both drugs. Plasma renin activity was significantly (P < 0.05) higher in captopril-treated rats (24.7 +/- 4.6 ng angiotensin I ml-1 h-1) than in either carvedilol-treated (7.9 +/- 1.4 ng angiotensin I m l-1 h-1) or control animals (7.4 +/- 1.0 ng angiotensin I ml-1 h-1). 4 Histological examination of the kidneys demonstrated a significantly reduced glomerular hypertrophy and glomerulosclerosis in those animals receiving carvedilol or captopril compared to controls. 5 Serum carve dilol concentration measured every 6 h for 24 h was variable and range d on average from 57 +/- 13 ng ml-1 at 16 h 00 min to 121 +/- 31 ng ml -1 at 03 h 00 min. These data indicate that the rats probably had 24 h systemic exposure to carvedilol. 6 The present study indicates that c arvedilol is effective in attenuating the progression of chronic renal failure in rats.