Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats

  • Authors:
    • Hideyuki Yamamoto
    • Daisuke Okuzaki
    • Kyosuke Yamanishi
    • Yunfeng Xu
    • Yuko Watanabe
    • Momoko Yoshida
    • Akifumi Yamashita
    • Naohisa Goto
    • Seiji Nishiguchi
    • Kazunori Shimada
    • Hiroshi Nojima
    • Teruo Yasunaga
    • Haruki Okamura
    • Hisato Matsunaga
    • Hiromichi Yamanishi
  • View Affiliations

  • Published online on: March 15, 2013     https://doi.org/10.3892/ijmm.2013.1304
  • Pages: 1057-1065
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Abstract

Spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) are frequently used as model rats not only in studies of essential hypertension and stroke, but also in studies of attention deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto rats (WKY) are normally used as controls in these studies. In this study, using these rats, we aimed to identify the genes causing hypertension and stroke, as well as the genes involved in ADHD. Since adrenal gland products can directly influence cardiovascular, endocrine and sympathetic nervous system functions, gene expression profiles in the adrenal glands of the 3 rat strains were examined using genome-wide microarray technology when the rats were 3 and 6 weeks of age, a period in which the rats are considered to be in a pre-hypertensive state. Gene expression profiles were compared between SHR and WKY and between SHRSP and SHR. A total of 353 genes showing more than a 4-fold increase or less than a 4-fold decrease in expression were isolated and candidate genes were selected as significantly enriched genes. SHR-specific genes isolated when the rats were 3 weeks of age contained 12 enriched genes related to transcriptional regulatory activity and those isolated when the rats were 6 weeks of age contained 6 enriched genes related to the regulation of blood pressure. SHRSP-specific genes isolated when the rats were 3 weeks of age contained 4 enriched genes related to the regulation of blood pressure and those isolated when the rats were 6 weeks of age contained 4 enriched genes related to the response to steroid hormone stimulus. Ingenuity pathway analysis of enriched SHR-specific genes revealed that 2 transcriptional regulators, cAMP responsive element modulator (Crem) and Fos-like antigen 1 (Fosl1), interact with blood pressure-regulating genes, such as neurotensin (Nts), apelin (Apln) and epoxide hydrolase 2, cytoplasmic (Ephx2). Similar analyses of SHRSP-specific genes revealed that angiotensinogen (Agt), one of the blood pressure-regulating genes, plays pivotal roles among SHRSP-specific genes. Moreover, genes associated with ADHD, such as low density lipoprotein receptor (Ldlr) and Crem, are discussed.
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May 2013
Volume 31 Issue 5

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

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Spandidos Publications style
Yamamoto H, Okuzaki D, Yamanishi K, Xu Y, Watanabe Y, Yoshida M, Yamashita A, Goto N, Nishiguchi S, Shimada K, Shimada K, et al: Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats. Int J Mol Med 31: 1057-1065, 2013
APA
Yamamoto, H., Okuzaki, D., Yamanishi, K., Xu, Y., Watanabe, Y., Yoshida, M. ... Yamanishi, H. (2013). Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats. International Journal of Molecular Medicine, 31, 1057-1065. https://doi.org/10.3892/ijmm.2013.1304
MLA
Yamamoto, H., Okuzaki, D., Yamanishi, K., Xu, Y., Watanabe, Y., Yoshida, M., Yamashita, A., Goto, N., Nishiguchi, S., Shimada, K., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats". International Journal of Molecular Medicine 31.5 (2013): 1057-1065.
Chicago
Yamamoto, H., Okuzaki, D., Yamanishi, K., Xu, Y., Watanabe, Y., Yoshida, M., Yamashita, A., Goto, N., Nishiguchi, S., Shimada, K., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats". International Journal of Molecular Medicine 31, no. 5 (2013): 1057-1065. https://doi.org/10.3892/ijmm.2013.1304