Effect of olmesartan on tissue expression balance between angiotensin II receptor and its inhibitory binding molecule

Hypertension
Atsu-Ichiro ShigenagaSatoshi Umemura

Abstract

We previously cloned a novel molecule interacting with angiotensin II (Ang II) type 1 receptor protein (ATRAP) and showed it to be an endogenous inhibitor of Ang II type 1 receptor signaling in cardiovascular cells. In this study, we tested a hypothesis that the balance of tissue expression of ATRAP and Ang II type 1 receptor is regulated in a tissue-specific manner during the development of hypertension and related cardiac hypertrophy. Concomitant with blood pressure increase and cardiac hypertrophy in spontaneously hypertensive rats, there was a constitutive decrease in the ratio of cardiac expression of ATRAP to Ang II type 1 receptor. However, treatment with olmesartan, an Ang II type 1 receptor-specific antagonist, either at a depressor or subdepressor dose, recovered the suppressed cardiac ATRAP to Ang II type 1 receptor ratio, which was accompanied by a decrease in Ang II type 1 receptor density, an inhibition of p38 mitogen-activated protein kinase activity, and a regression of cardiac hypertrophy. Furthermore, Ang II stimulation suppressed the ATRAP to Ang II type 1 receptor ratio with hypertrophic responses in both the cardiomyocytes and rat hearts. These findings show a tissue-specific regulatory balancing of the exp...Continue Reading

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Citations

May 9, 2013·The Journal of Biological Chemistry·Miyuki MatsudaSatoshi Umemura
May 17, 2014·International Journal of Medical Sciences·Akinobu MaedaSatoshi Umemura
Mar 25, 2017·International Journal of Molecular Sciences·Kohji OhkiKouichi Tamura
Nov 12, 2009·The Journal of Pharmacology and Experimental Therapeutics·Marcus BaumannUwe Heemann
Aug 27, 2010·American Journal of Physiology. Renal Physiology·Hiromichi WakuiSatoshi Umemura
Apr 16, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bhama RamkhelawonStephanie Lehoux

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