ARB and Cardioprotection

作者：Akazawa Hiroshi; Yabumoto Chizuru; Yano Masamichi; Kudo Sakamoto Yoko; Komuro Issei^*

来源：Cardiovascular Drugs and Therapy, 2013, 27(2): 155-160.

DOI：10.1007/s10557-012-6392-2

• Constitutive activity
• Cardiac remodeling
• G protein-coupled receptor
• Inverse agonist
• Mechanical stress

A growing body of evidence has suggested that the use of angiotensin II (Ang II) type 1 (AT(1)) receptor blockers (ARBs) leads to a significant decrease in mortality and morbidity in patients with congestive heart failure. The AT(1) 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 AT(1) receptor. However, recent in vitro studies have demonstrated that AT(1) 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 AT(1) receptor by inducing conformational switch without the involvement of Ang II. Experimental studies have demonstrated that Ang II-independent activation of AT(1) receptor is profoundly relevant to the pathogenesis of cardiac remodeling in vivo, and that these agonist-independent activities of AT(1) 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 AT(1) receptor.

• 出版日期2013-4