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. Six weeks following partial renal ablation, the urinary protein excretion 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 +/- 27 mg d-1). 3. Serum creatinine (Scr) and urea nitrogen (SUN) concentrations 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 improved 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 ml-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 carvedilol concentration measured every 6 h for 24 h was variable and ranged 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 carvedilol is effective in attenuating the progression of chronic renal failure in rats.

Effect of fenoldopam in dogs with spontaneous renal insufficiency.

Fenoldopam administration orally or i.v. resulted in significant increases in paraaminohippuric acid (PAH) clearance in both four control dogs and four dogs with chronic renal failure. Oral fenoldopam resulted in significant plasma levels of fenoldopam sulfate metabolites. One metabolite, fenoldopam-8-sulfate, a potential inhibitor of organic anion transport, did not depress renal cortical slice accumulation of PAH. The data therefore indicate that in dogs with chronic renal failure, PAH clearance after fenoldopam administration is a reliable measure of renal plasma flow, and fenoldopam can result in an increase in renal plasma flow.