Renal Protective Effect of Candesartan Cilexetil in Spontaneously Hypercholesterolemic Rats

The Japanese Journal of Pharmacology

Masayuki Ohta¹  Yoshimi Imura²  Takanori Matsuo²  Eiichiro Ishikawa²  Yasuo Sugiyama²  Yumiko Shibouta¹  Yoshimasa Ishimura³ 

[1] Research Management Department, Takeda Chemical Industries Ltd.;Pharmacology Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries Ltd.;Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd.

关键词: Candesartan cilexetil;    Renal protective effect;    Spontaneously hypercholesterolemic rat;    Angiotensin II;    AT1-receptor antagonist;   

DOI  :  10.1254/jjp.88.300

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(20)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.

【 授权许可】

Unknown