Carvedilol protects against glomerulosclerosis in rat remnant kidney without general changes in antioxidant enzyme status. A comparative study of two beta-blocking drugs, carvedilol and propanolol.
Nephron loss leads to increased production of reactive oxygen intermediates. 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) production in rats with chronic renal failure caused by 5/6 nephrectomy (remnant 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 glomerulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentration in cortex homogenates, was decreased in carvedilol-treated rats only. Superior beneficial effect of carvedilol treatment is not linked to a significant up-regulation of the activities of the remnant kidney antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) or to a decreased in vivo H2O2 production.
Van den Branden
C
C
Menselijke Anatomie & Embryologie, Vrije Universiteit Brussels, Belgium.
Gabriels
M
M
Vamecq
J
J
Vanden Houte
K
K
Verbeelen
D
D
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D016166:Free Radical Scavengers / Q000378:metabolism / Q000627:therapeutic use*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009392:Nephrectomy; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D000447:Aldehydes; D000975:Antioxidants; D002227:Carbazoles; D016166:Free Radical Scavengers; D011412:Propanolamines; D000077261:Carvedilol; D008315:Malondialdehyde; D011433:Propranolol; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal