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.
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Short
B G
BG
Cyronak
M J
MJ
Contino
L C
LC
DiCristo
M
M
Wang
Y X
YX
Ruffolo
R R
RR
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002227:Carbazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000209:etiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011412:Propanolamines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D002216:Captopril; D003404:Creatinine