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Article

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 / Copyright

    Affiliations: Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, DNA-Chip Development Center for Infectious Diseases, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Genome Informatics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565‑0871, Japan, Hirakata General Hospital for Developmental Disorders, Hirakata, Osaka 573-0122, Japan
  • Pages: 1057-1065
    |
    Published online on: March 15, 2013
       https://doi.org/10.3892/ijmm.2013.1304
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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