Abstract |
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.
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Authors | Qi-Sheng Ling, Sai-Long Zhang, Jia-Sheng Tian, Ming-He Cheng, Ai-Jun Liu, Feng-Hua Fu, Jian-Guo Liu, Chao-Yu Miao |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 42
Issue 6
Pg. 871-884
(Jun 2021)
ISSN: 1745-7254 [Electronic] United States |
PMID | 34002042
(Publication Type: Journal Article)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Antihypertensive Agents
- Biphenyl Compounds
- Imidazoles
- allisartan isoproxil
- Aldosterone
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Topics |
- Aldosterone
(metabolism)
- Angiotensin II Type 1 Receptor Blockers
(therapeutic use)
- Animals
- Antihypertensive Agents
(therapeutic use)
- Aorta
(drug effects)
- Aortic Diseases
(complications, mortality, prevention & control)
- Biphenyl Compounds
(therapeutic use)
- Blood Pressure
(drug effects)
- Brain
(drug effects, pathology)
- Cerebrovascular Disorders
(complications, mortality, pathology, prevention & control)
- Heart
(drug effects)
- Hypertension
(complications, mortality)
- Imidazoles
(therapeutic use)
- Kaplan-Meier Estimate
- Kidney
(drug effects, pathology, surgery)
- Myocardium
(pathology)
- Oxidative Stress
(drug effects)
- Rats, Sprague-Dawley
- Stroke
(complications, mortality, prevention & control)
- Rats
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