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ARB and Cardioprotection

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Abstract

A growing body of evidence has suggested that the use of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) leads to a significant decrease in mortality and morbidity in patients with congestive heart failure. The AT1 receptor is a seven-transmembrane G protein-coupled receptor, and is involved in regulating the physiological and pathological process of the cardiovascular system. Systemically and locally generated Ang II has agonistic action on AT1 receptor. However, recent in vitro studies have demonstrated that AT1 receptor is structurally flexible and instable, and has significant and varying levels of spontaneous activity in an Ang II-independent manner. Furthermore, mechanical stress activates AT1 receptor by inducing conformational switch without the involvement of Ang II. Experimental studies have demonstrated that Ang II-independent activation of AT1 receptor is profoundly relevant to the pathogenesis of cardiac remodeling in vivo, and that these agonist-independent activities of AT1 receptor can be inhibited by inverse agonists, but not by neutral antagonists. Therefore, inverse agonist activity emerges as an important pharmacological parameter that contributes to cardioprotective effects of ARBs through inhibiting both Ang II-dependent and -independent activation of AT1 receptor.

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Acknowledgements

This work was supported in part by grants from Japan Society for the Promotion of Science (KAKENHI 20390218, 21229010, 23390213) and Health and Labor Sciences Research Grants (to I.K. and H.A.), Takeda Science Foundation, The Uehara Memorial Foundation, The Ichiro Kanehara Foundation, and Suzuken Memorial Foundation (to H.A.).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hiroshi Akazawa, Chizuru Yabumoto, Masamichi Yano, Yoko Kudo-Sakamoto & Issei Komuro

  2. Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan

    Hiroshi Akazawa & Issei Komuro

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  1. Hiroshi Akazawa
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Correspondence to Issei Komuro.

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Akazawa, H., Yabumoto, C., Yano, M. et al. ARB and Cardioprotection. Cardiovasc Drugs Ther 27, 155–160 (2013). https://doi.org/10.1007/s10557-012-6392-2

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