Renal protective effect of candesartan cilexetil in spontaneously hypercholesterolemic rats.
Spontaneously hypercholesterolemic (SHC) rats exhibit hypercholesterolemia, proteinuria and focal glomerulosclerosis with age, and they finally die as a result of renal failure. In this study, the renoprotective effects of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, and enalapril, an angiotensin I converting enzyme inhibitor, were examined in SHC rats. Candesartan cilexetil (0.1 and 1 mg /kg) and enalapril (10 mg/kg) were administered orally to 10-week-old SHC rats for a 6-week period. Candesartan cilexetil (1 mg/kg) and enalapril (10 mg/kg) significantly inhibited proteinuria and hypercholesterolemia to a similar extent. In untreated 16-week-old SHC rats, glomerulosclerosis, basophilic change, cast formation and interstitial mononuclear cell infiltration were observed. Candesartan cilexetil (1 mg/kg) inhibited all of these histological changes. Enalapril inhibited glomerulosclerosis and cast formation. These results show that candesartan cilexetil and enalapril have renal protective effects in SHC rats. Thus, angiotensin II might play an important role in renal pathogenesis in a model of focal glomerulosclerosis with hypercholesterolemia.
Matsuo
Takanori
T
Pharmaceutical Research Division, Takeda Chemical Industries Ltd, Osaka, Japan.
Ishikawa
Eiichiro
E
Ohta
Masayuki
M
Shibouta
Yumiko
Y
Ishimura
Yoshimasa
Y
Imura
Yoshimi
Y
Sugiyama
Yasuo
Y
D000419:Albuminuria / Q000517:prevention & control; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004656:Enalapril / Q000627:therapeutic use; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000517:prevention & control; D006937:Hypercholesterolemia / Q000150:complications / Q000517:prevention & control*; D007202:Indicators and Reagents; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007202:Indicators and Reagents; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D004656:Enalapril; D002784:Cholesterol; C077793:candesartan cilexetil