Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms

  • Authors:
    • Yakun Zhao
    • Qingguo Zhu
    • Shiping Sun
    • Yu Qiu
    • Jingquan Li
    • Wei Liu
    • Gangjun Yuan
    • Hua Ma
  • View Affiliations

  • Published online on: January 29, 2018     https://doi.org/10.3892/ijmm.2018.3435
  • Pages: 2375-2388
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Abstract

Hypertension is one of the most common complications following renal transplantation, and it increases the risk of graft loss and other cardiovascular diseases. Previous studies have revealed that the use of angiotensin II (Ang II) blockers for preventing and treating hypertension is closely associated with higher survival following renal transplantation. However, the cellular and molecular mechanisms by which the vascular contractility of the recipient is altered in response to Ang II following renal transplantation have not been fully elucidated. In the present study, using the Fisher‑Lewis rat kidney transplantation model, the blood pressure (BP) of the conscious transplant recipient was measured following the intravenous administration of Ang II. In addition, the mechanisms underlying the Ang II-mediated vascular contractility via the type 1 and type 2 Ang II receptors (AT1R and AT2R, respectively) in large and small-resistance blood vessels were determined in the recipient after renal transplantation. The results showed that renal transplantation significantly increased the Ang II-stimulated BP of the rats. Additionally, ex vivo contractility experiments using aorta and mesenteric arteries revealed that the contractions induced by Ang II were significantly strengthened in the recipient following renal transplantation, and were associated with an increased intracellular Ca2+ concentration. Losartan almost eradicated the Ang II-induced contractions whereas PD-123319 had no apparent effects on the Ang II-induced contractions in the aorta and mesenteric arteries of the recipient. Furthermore, the expression levels of AT1R but not AT2R were significantly increased in the vasculature of the recipient following renal transplantation, which exhibited a close association with selective DNA demethylation detected in the promoter region of the vascular AT1aR gene. These results indicate that changes of recipient vascular AT1R gene expression, occurring through a mechanism involving DNA methylation, increase the vascular contractility in response to Ang II. This may lead to the increased risk of hypertension following renal transplantation.
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April-2018
Volume 41 Issue 4

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

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Spandidos Publications style
Zhao Y, Zhu Q, Sun S, Qiu Y, Li J, Liu W, Yuan G and Ma H: Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms. Int J Mol Med 41: 2375-2388, 2018
APA
Zhao, Y., Zhu, Q., Sun, S., Qiu, Y., Li, J., Liu, W. ... Ma, H. (2018). Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms. International Journal of Molecular Medicine, 41, 2375-2388. https://doi.org/10.3892/ijmm.2018.3435
MLA
Zhao, Y., Zhu, Q., Sun, S., Qiu, Y., Li, J., Liu, W., Yuan, G., Ma, H."Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms". International Journal of Molecular Medicine 41.4 (2018): 2375-2388.
Chicago
Zhao, Y., Zhu, Q., Sun, S., Qiu, Y., Li, J., Liu, W., Yuan, G., Ma, H."Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms". International Journal of Molecular Medicine 41, no. 4 (2018): 2375-2388. https://doi.org/10.3892/ijmm.2018.3435