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

Authors: Shigenaga, A  Tamura, K  Wakui, H  Masuda, S  Azuma, K  Tsurumi-Ikeya, Y  Ozawa, M  Mogi, M  Matsuda, M  Uchino, K  Kimura, K  Horiuchi, M  Umemura, S 
Citation: Shigenaga A, etal., Hypertension. 2008 Oct;52(4):672-8. Epub 2008 Aug 25.
Pubmed: (View Article at PubMed) PMID:18725581
DOI: Full-text: DOI:10.1161/HYPERTENSIONAHA.108.117341

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 expression of ATRAP and Ang II type 1 receptor during the development of hypertension and cardiac remodeling and further suggest that the upregulation of the tissue ATRAP to Ang II type 1 receptor ratio may be one of the therapeutic benefits of olmesartan beyond its blood pressure-lowering effect.

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CRRD Object Information
CRRD ID: 2314351
Created: 2009-11-11
Species: All species
Last Modified: 2009-11-11
Status: ACTIVE



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