Allisartan isoproxil reduces mortality of stroke-prone rats and protects against cerebrovascular,cardiac,and aortic damage

• 作者: Qi-sheng Ling Sai-long Zhang Jia-sheng Tian Ming-he Cheng Ai-jun Liu Feng-hua Fu Jian-guo Liu Chao-yu Miao
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: Cardiovascular Pharmacology
• 页码范围: 871-884
• 页数: 14页
• 语种: 英文

摘要

Stroke is a common cause of death and disability.Allisartan isoproxil(ALL)is a new angiotensin Ⅱ receptor blocker and a new antihypertensive drug discovered and developed in China.In the present study we investigated the therapeutic effects of ALL in stroke-prone renovascular hypertensive rats(RHR-SP)and the underlying mechanisms.The model rats were generated via two-kidney two-clip(2K2C)surgery,which led to 100％of hypertension,100％of cerebrovascular damage as well as 100％of mortality 1 year after the surgery.Administration of ALL(30 mg·kg-1·d-1 in diet,for 55 weeks)significantly decreased stroke-related death and prolonged lifespan in RHR-SP,but the survival ALL-treated RHR-SP remained of hypertension and cardiovascular hypertrophy compared with sham-operated normal controls.In addition to cardiac,and aortic protection,ALL treatment for 10 or 12 weeks significantly reduced cerebrovascular damage incidence and scoring,along with a steady reduction of blood pressure(BP)in RHR-SP.Meanwhile,it significantly decreased serum aldosterone and malondialdehyde levels and cerebral NAD(P)H oxidase expressions in RHR-SP.We conducted 24 h continuous BP recording in conscious freely moving RHR-SP,and found that a single intragastric administration of ALL produced a long hypotensive effect lasting for at least 12 h on systolic BP.Taken together,our results in RHR-SP demonstrate that ALL can be used for stroke prevention via BP reduction and organ protection,with the molecular mechanisms related to inhibition of angiotensin-aldosterone system and oxidative stress.This study also provides a valuable scoring for evaluation of cerebrovascular damage and drug efficacy.