Protective effects of candesartan cilexetil (TCV-116) against stroke, kidney dysfunction and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats

被引:99
作者
Inada, Y
Wada, T
Ojima, M
Sanada, T
Shibouta, Y
Kanagawa, R
Ishimura, Y
Fujisawa, Y
Nishikawa, K
机构
[1] TAKEDA CHEM IND LTD, DRUG SAFETY RES LABS, DIV PHARMACEUT RES, OSAKA 532, JAPAN
[2] TAKEDA CHEM IND LTD, MOL PHARMACOL LABS, DIV PHARMACEUT RES, OSAKA 532, JAPAN
关键词
organ damages; stroke-prone spontaneously hypertensive rats(SHRSP); renin-angiotensin system; renal mRNA; candesartan cilexetil; TCV-116; enalapril;
D O I
10.3109/10641969709083206
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of chronic treatment with an angiotensin II receptor antagonist, candesartan cilexetil (TCV-116, 0.1, 1, 10 mg/kg), and an angiotensin converting enzyme inhibitor, enalapril maleate (enalapril, 10 mg/kg), on the development of end-organ damage were examined in stroke-prone spontaneously hypertensive rats (SHRSP). The control SHRSP developed severe hypertension with stroke signs and increased urinary protein excretion, TCV-116 (0.1 mg/kg) reduced the stroke incidence and urinary protein excretion without affecting the blood pressure. TCV-116 (1 and 10 mg/kg) and enalapril reduced blood pressure, the stroke incidence, the urinary indices and left ventricular weight. Circulating renin-angiotensin system (RAS) and renal renin mRNA expression were significantly accelerated or tended to be accelerated in the control SHRSP with end-organ damages. A low dose of TCV-116 tended to reduce the RAS indices in plasma by improving the damages, whereas a high dose (10 mg/kg) increased them by the reflexes with blocking RAS. The present results indicate that chronic All blockade reduces the increase in blood pressure, end-organ damages and RAS related to the damages in SHRSP.
引用
收藏
页码:1079 / 1099
页数:21
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