Abilities of candesartan and other AT1 receptor blockers to impair angiotensin II-induced AT1 receptor activation after wash-out

作者：Kiya Yoshihiro; Miura Shin ichiro^*; Matsuo Yoshino; Karnik Sadashiva S; Saku Keijiro

来源：Journal of the Renin-Angiotensin-Aldosterone System, 2012, 13(1): 76-83.

DOI：10.1177/1470320311417478

• Angiotensin II type 1 receptor blocker
• carboxyl group
• cell-based wash-out assay
• extracellular signal-regulated kinase activation
• inositol phosphate production
• effects

Angiotensin II (Ang II) binds to Ang II type 1 (AT1) receptor and evokes cell signaling, and subsequently stimulates vasoconstriction and cell proliferation, which eventually lead to cardiovascular disease. Since most AT1 receptor blockers (ARBs) have molecular (differential) effects, we evaluated the specific features of candesartan and compared the abilities of candesartan and other ARBs (olmesartan, telmisartan, valsartan, irbesartan and losartan) to bind to and activate AT1 receptors using a cell-based wash-out assay. Each ARB blocked Ang II-induced extracellular signal-regulated kinase (ERK) activation and inositol phosphate production to different degrees after wash-out. In addition, a small difference in the molecular structure, i.e. a carboxyl group, between candesartan and candesartan-7H was associated with a difference in the degree of this blocking effect. In addition, interaction between Gln257 in the AT1 receptor and the carboxyl group of candesartan may be partially associated with the effect of candesartan after wash-out. Although our findings regarding the molecular effects of ARB are based on basic research, these findings may lead to an exciting new area in the clinical application of ARBs.

• 出版日期2012-3