Effects of TCV-116 on Endothelin-1 and PDGF A-Chain Expression in Angiotensin II-Induced Hypertensive Rats

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Author(s)

    • HARA Kazuyoshi
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
    • KOBAYASHI Naohiko
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
    • NAKANO Shigefumi
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
    • MORI Yousuke
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
    • TSUBOKOU Yusuke
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
    • MATSUOKA Hiroaki
    • Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine

Abstract

Angiotensin II (Ang II) has been shown to stimulate cardiac growth and collagen synthesis in cultured vascular smooth muscle cells and to increase fibroblast proliferation. Chronic infusion with Ang II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart. This study investigated the effects of an Ang II type 1 receptor antagonist, TCV-116, on preproendothelin-1 (preproET-1), ET<SUB>A</SUB> receptor and platelet-derived growth factor (PDGF) A-chain expression in the left ventricle of Wistar-Kyoto rats treated for 2 weeks with Ang II (200ng·kg<SUP>-1</SUP>·min<SUP>-1</SUP>), and the relation of these effects to myocardial remodeling. Rats given Ang II alone (ANGII-V) were compared with rats also receiving TCV-116 (ANGII-TCV). In both groups, blood pressure was similar and significantly higher than in control rats. The preproET-1, ET<SUB>A</SUB> receptor and PDGF A-chain expressions in the left ventricle were significantly increased in ANGII-V compared with control rats, and were significantly suppressed in ANGII-TCV compared with ANGII-V rats. ANGII-V rats showed a significant increase of the type I collagen expression, wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all these parameters being significantly improved by TCV-116. Myocardial remodeling in Ang II-induced hypertensive rats was significantly ameliorated by a subdepressor dose to TCV-116, which may have been due to a decrease in ET-1 and PDGF A-chain expression in the left ventricle. (Hypertens Res 2001; 24: 55-64)

Journal

  • Hypertension Research

    Hypertension Research 24(1), 55-64, 2001-01-01

    The Japanese Society of Hypertension

References:  53

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008742024
  • NII NACSIS-CAT ID (NCID)
    AA10847079
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09169636
  • Data Source
    CJP  CJPref  J-STAGE 
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