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Attenuation of angiotensin II-induced hypertension and cardiac hypertrophy in transgenic mice overexpressing a type 1 receptor mutant.

Authors: Ahmad, S  Cesana, F  Lamperti, E  Gavras, H  Yu, J 
Citation: Ahmad S, etal., Am J Hypertens. 2009 Dec;22(12):1320-5. doi: 10.1038/ajh.2009.181. Epub 2009 Sep 24.
Pubmed: (View Article at PubMed) PMID:19779471
DOI: Full-text: DOI:10.1038/ajh.2009.181

BACKGROUND: The angiotensin II (AngII) type 1 receptor (AT1) regulates cardiovascular function by activating various signal pathways. The purpose of this study was to evaluate the effects of a mutant AT1 receptor on AngII-responding blood pressure and cardiac hypertrophy in conjunction with altered AngII activation of RhoA and Akt. METHODS: A mutant AT1 receptor was constructed and overexpressed in C57BL mice using a ubiquitous-expression vector pCAGGS. The phenotype and signal transduction of the transgenic (TG) mice were compared with the wild-type (WT) mice. RESULTS: The TG mice showed a similar baseline phenotype as WT mice, but their blood pressure in response to continuous AngII infusion was significantly lower, as measured on days 3, 4, 7, and 14, with a difference of 20 mm Hg by day 14. There was also a significantly larger heart-to-total-body-weight ratio in the WT mice, whose heart weight (HW) was 0.441 +/- 0.008% of total body weight (BW) compared to the TG mice at 0.416 +/- 0.008%. Aortic endothelial cells isolated from these TG mice displayed an altered signaling profile, such as diminished activation of Akt and RhoA in response to AngII. In contrast, Galphaq coupling and ERK/JNK activation did not change. CONCLUSION: The expression of an AT1 mutant receptor in the presence of WT receptor can effectively modulate AngII-effected signaling. Furthermore, the elimination of Akt and RhoA activation by AngII significantly reduces but does not eliminate its hypertensive effect.


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CRRD Object Information
CRRD ID: 8548902
Created: 2014-03-25
Species: All species
Last Modified: 2014-03-25
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.