Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan

  • Authors:
    • Yoshikazu Fujiwara
    • Suguru Shiraya
    • Takashi Miyake
    • Satoshi Yamakawa
    • Motokuni Aoki
    • Hirofumi Makino
    • Motonobu Nishimura
    • Ryuichi Morishita
  • View Affiliations

  • Published online on: December 1, 2008     https://doi.org/10.3892/ijmm_00000075
  • Pages: 703-708
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Abstract

Angiotensin (Ang) II exerts direct effects on the arterial wall to influence atherosclerosis and aneurysm development with the induction of vascular inflammation. Therefore, we examined the hypothesis that the inhibition of Ang II would decrease the expansion of abdominal aortic aneurysm (AAA) in a rat model. We used the Ang II receptor blocker (ARB) valsartan to inhibit the effect of Ang II. Additionally, we employed a dosage of valsartan (1 mg/ kg/day) that does not affect blood pressure, to avoid the effect of blood pressure lowering. Notably, progression of elastase-induced AAA was inhibited in rats treated with valsartan (P≤0.05). To clarify the mechanism, we focused on matrix metalloproteases (MMPs) and inflammatory related factors. Western blot analysis demonstrated that the expression of MMPs was significantly decreased in an AAA model treated with continuous ARB infusion compared to an AAA model treated with vehicle (P≤0.05), through suppression of nuclear factor κB activation (P≤0.05). Consistently, valsartan significantly inhibited infiltration of macrophages into the aortic wall, accompanied by a reduction of protein expression of intercellular adhesion molecule-1. Importantly, the inhibitory effect of valsartan on MMP-2 and MMP-9 expression was also confirmed using isolated peritoneal macrophages from a rat AAA model. Moreover, treatment with valsartan protected against the destruction of elastic fibers. Overall, the present study demonstrated that treatment with valsartan, significantly prevented the progression of experimental AAA in a rat model. These data suggest that blockade of Ang II has an inhibitory effect on the development of AAA, independent of its antihypertensive effect.

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December 2008
Volume 22 Issue 6

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

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Spandidos Publications style
Fujiwara Y, Shiraya S, Miyake T, Yamakawa S, Aoki M, Makino H, Nishimura M and Morishita R: Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan. Int J Mol Med 22: 703-708, 2008
APA
Fujiwara, Y., Shiraya, S., Miyake, T., Yamakawa, S., Aoki, M., Makino, H. ... Morishita, R. (2008). Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan. International Journal of Molecular Medicine, 22, 703-708. https://doi.org/10.3892/ijmm_00000075
MLA
Fujiwara, Y., Shiraya, S., Miyake, T., Yamakawa, S., Aoki, M., Makino, H., Nishimura, M., Morishita, R."Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan". International Journal of Molecular Medicine 22.6 (2008): 703-708.
Chicago
Fujiwara, Y., Shiraya, S., Miyake, T., Yamakawa, S., Aoki, M., Makino, H., Nishimura, M., Morishita, R."Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan". International Journal of Molecular Medicine 22, no. 6 (2008): 703-708. https://doi.org/10.3892/ijmm_00000075