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Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats

  • Authors:
    • De-Hua He
    • Liang-Min Zhang
    • Li-Ming Lin
    • Ruo-Bing Ning
    • Hua-Jun Wang
    • Chang-Sheng Xu
    • Jin-Xiu Lin

  • View Affiliations

  • Published online on: December 10, 2013     https://doi.org/10.3892/ijmm.2013.1583
  • Pages: 301-309

  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate ⅰ) whether short‑ and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ⅱ) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week‑old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short‑ and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short‑ and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive populations in order to prevent BP-linked brain damage.
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2014-February
Volume 33 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Journal Metrics
  • Impact Factor: 5.7
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 12.3
  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
He D, Zhang L, Lin L, Ning R, Wang H, Xu C and Lin J: Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats. Int J Mol Med 33: 301-309, 2014.
APA
He, D., Zhang, L., Lin, L., Ning, R., Wang, H., Xu, C., & Lin, J. (2014). Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats. International Journal of Molecular Medicine, 33, 301-309. https://doi.org/10.3892/ijmm.2013.1583
MLA
He, D., Zhang, L., Lin, L., Ning, R., Wang, H., Xu, C., Lin, J."Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats". International Journal of Molecular Medicine 33.2 (2014): 301-309.
Chicago
He, D., Zhang, L., Lin, L., Ning, R., Wang, H., Xu, C., Lin, J."Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats". International Journal of Molecular Medicine 33, no. 2 (2014): 301-309. https://doi.org/10.3892/ijmm.2013.1583