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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 / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of Xiamen University, Fuzhou, Fujian, P.R. China, Department of Cardiology, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, P.R. China, Department of Cardiology, Affiliated Hospital of Putian College, Fuzhou, Fujian, P.R. China, Fujian Institute of Hypertension, Fuzhou, Fujian, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 301-309
    |
    Published online on: December 10, 2013
       https://doi.org/10.3892/ijmm.2013.1583
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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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1 

Chobanian AV, Bakris GL, Black HR, et al: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 289:2560–2572. 2003. View Article : Google Scholar

2 

Chobanian AV, Bakris GL, Black HR, et al: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 42:1206–1252. 2003. View Article : Google Scholar

3 

Sun Z, Zheng L, Detrano R, et al: Risk of progression to hypertension in a rural Chinese women population with prehypertension and normal blood pressure. Am J Hypertens. 23:627–632. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Vasan RS, Larson MG, Leip EP, Kannel WB and Levy D: Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet. 358:1682–1686. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Greenlund KJ, Croft JB and Mensah GA: Prevalence of heart disease and stroke risk factors in persons with prehypertension in the United States, 1999–2000. Arch Intern Med. 164:2113–2118. 2004.PubMed/NCBI

6 

Mainous AG III, Everett CJ, Liszka H, King DE and Egan BM: Prehypertension and mortality in a nationally representative cohort. Am J Cardiol. 94:1496–1500. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Maillard P, Seshadri S, Beiser A, et al: Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol. 11:1039–1047. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Julius S, Nesbitt SD, Egan BM, et al: Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 354:1685–1697. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Yambe M, Tomiyama H, Yamada J, et al: Arterial stiffness and progression to hypertension in Japanese male subjects with high normal blood pressure. J Hypertens. 25:87–93. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Baumann M, Janssen BJ, Hermans JJ, et al: Transient AT1 receptor-inhibition in prehypertensive spontaneously hypertensive rats results in maintained cardiac protection until advanced age. J Hypertens. 25:207–215. 2007. View Article : Google Scholar

11 

Peng F, Lin J, Lin L and Tang H: Transient prehypertensive treatment in spontaneously hypertensive rats: A comparison of losartan and amlodipine regarding long-term blood pressure, cardiac and renal protection. Int J Mol Med. 30:1376–1386. 2012.

12 

Vacher E, Richer C and Giudicelli JF: Effects of losartan on cerebral arteries in stroke-prone spontaneously hypertensive rats. J Hypertens. 14:1341–1348. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Yamori Y, Horie R, Akiguchi I, Kihara M, Nara Y and Lovenberg W: Symptomatological classification in the development of stroke in stroke-prone spontaneously hypertensive rats. Jpn Circ J. 46:274–283. 1982. View Article : Google Scholar : PubMed/NCBI

14 

Wu Y and Song W: Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis. FASEB J. 27:208–221. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H and Takeshita A: Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation. 109:2357–2362. 2004. View Article : Google Scholar

16 

Ito H, Torii M and Suzuki T: A comparative study on lipid peroxidation in cerebral cortex of stroke-prone spontaneously hypertensive and normotensive rats. Int J Biochem. 25:1801–1805. 1993.PubMed/NCBI

17 

Yu L, Quinn MT, Cross AR and Dinauer MC: Gp91(phox) is the heme binding subunit of the superoxide-generating NADPH oxidase. Proc Natl Acad Sci USA. 95:7993–7998. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Tang J, Liu J, Zhou C, et al: Role of NADPH oxidase in the brain injury of intracerebral hemorrhage. J Neurochem. 94:1342–1350. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Fujii J and Taniguchi N: Down regulation of superoxide dismutases and glutathione peroxidase by reactive oxygen and nitrogen species. Free Radic Res. 31:301–308. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Phillips MI and de Oliveira EM: Brain renin angiotensin in disease. J Mol Med (Berl). 86:715–722. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Wright JW and Harding JW: The brain renin-angiotensin system: a diversity of functions and implications for CNS diseases. Pflugers Arch. 465:133–151. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Gao L, Wang WZ, Wang W and Zucker IH: Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla: potential mechanism for sympathetic overactivity in heart failure. Hypertension. 52:708–714. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Takeda-Matsubara Y, Matsubara K, Ochi H, Ito M, Iwai M and Horiuchi M: Expression of endothelial angiotensin II receptor mRNA in pregnancy-induced hypertension. Am J Hypertens. 16:993–999. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Ganten D, Marquez-Julio A, Granger P, et al: Renin in dog brain. Am J Physiol. 221:1733–1737. 1971.PubMed/NCBI

25 

Fischer-Ferraro C, Nahmod VE, Goldstein DJ and Finkielman S: Angiotensin and renin in rat and dog brain. J Exp Med. 133:353–361. 1971. View Article : Google Scholar : PubMed/NCBI

26 

Hamaguchi R, Takemori K, Inoue T, Masuno K and Ito H: Short-term treatment of stroke-prone spontaneously hypertensive rats with an AT1 receptor blocker protects against hypertensive end-organ damage by prolonged inhibition of the renin-angiotensin system. Clin Exp Pharmacol Physiol. 35:1151–1155. 2008. View Article : Google Scholar

27 

Takemori K, Ishida H and Ito H: Continuous inhibition of the renin-angiotensin system and protection from hypertensive end-organ damage by brief treatment with angiotensin II type 1 receptor blocker in stroke-prone spontaneously hypertensive rats. Life Sci. 77:2233–2245. 2005. View Article : Google Scholar

28 

Ichiki T: Regulation of angiotensin II receptor expression. Curr Pharm Des. 19:3013–3021. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Mogi M and Horiuchi M: Effect of angiotensin II type 2 receptor on stroke, cognitive impairment and neurodegenerative diseases. Geriatr Gerontol Int. 13:13–18. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Steckelings UM, Paulis L, Namsolleck P and Unger T: AT2 receptor agonists: hypertension and beyond. Curr Opin Nephrol Hypertens. 21:142–146. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Muradian K and Schachtschabel DO: The role of apoptosis in aging and age-related disease: update. Z Gerontol Geriatr. 34:441–446. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Mattson MP: Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 1:120–129. 2000. View Article : Google Scholar

33 

Hamet P, Richard L, Dam TV, et al: Apoptosis in target organs of hypertension. Hypertension. 26:642–648. 1995. View Article : Google Scholar : PubMed/NCBI

34 

Kannan K and Jain SK: Oxidative stress and apoptosis. Pathophysiology. 7:153–163. 2000. View Article : Google Scholar

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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