In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2008-10), p. 672-678
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 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.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/HYPERTENSIONAHA.108.117341
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2008
detail.hit.zdb_id:
2094210-2
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