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Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

Item Type:Article
Title:Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy
Creators Name:Hoffmann, S. and Krause, T. and van Geel, P.P. and Willenbrock, R. and Pagel, I. and Pinto, Y.M. and Buikema, H. and van Gilst, W.H. and Lindschau, C. and Paul, M. and Inagami, T. and Ganten, D. and Urata, H.
Abstract:Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT 1 receptors. However, the role of myocardial AT 1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that increased myocardial AT 1 receptor density causes cardiac hypertrophy apart from high blood pressure we developed a transgenic rat model which expresses the human AT 1 receptor under the control of the α-myosin heavy-chain promoter specifically in the myocardium. Expression was identified and quantified by northern blot analysis and radioligand binding assays, demonstrating overexpression of angiotensin II receptors in the transgenic rats up to 46 times the amount seen in nontransgenic rats. Coupling of the human AT 1 receptor to rat G proteins and signal transduction cascade was verified by sensitivity to GTP-γ-S and increased sensitivity of intracellular Ca 2+ [Ca 2+] i to angiotensin II in fluo-3 loaded transgenic cardiomyocytes. Transgenic rats exhibited normal cardiac growth and function under baseline conditions. Pronounced hypertrophic growth and contractile responses to angiotensin II, however, were noted in transgenic rats challenged by volume and pressure overload. In summary, we generated a new transgenic rat model that exhibits an upregulated myocardial AT 1 receptor density and demonstrates augmented cardiac hypertrophy and contractile response to angiotensin II after volume and pressure overload, but not under baseline conditions.
Keywords:Angiotensin II Receptors, Heart Hypertrophy, Transgenic Rats, Animals, Rats
Source:Journal of Molecular Medicine
ISSN:0946-2716
Publisher:Springer (Germany)
Volume:79
Number:10
Page Range:601-608
Date:1 January 2001
Official Publication:https://doi.org/10.1007/s001090100246
PubMed:View item in PubMed

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