Cardiac-specific overexpression of the human type 1 angiotensin II receptor causes delayed repolarization.

@article{Rivard2008CardiacspecificOO,
  title={Cardiac-specific overexpression of the human type 1 angiotensin II receptor causes delayed repolarization.},
  author={Katy Rivard and Pierre Paradis and Mona Nemer and C{\'e}line Fiset},
  journal={Cardiovascular research},
  year={2008},
  volume={78 1},
  pages={
          53-62
        }
}
AIMS Mice with cardiac-specific overexpression of human angiotensin II type 1 receptor (AT1R) undergo cardiac remodelling and die prematurely of sudden death. Since excessive QT prolongation is a major risk factor for ventricular arrhythmias and sudden death, we hypothesize that chronic stimulation of AT1R might contribute to sudden death by promoting delayed repolarization and ventricular arrhythmias. METHODS In the present study, a detailed analysis of ventricular repolarization parameters… 
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The data show that cardiac contractility and the mechanisms that underlie excitation-contraction coupling are altered in AT(1)R mice, and since the alterations in contractility occur before the development of cardiac hypertrophy, it is likely that these changes are attributable to the increased activity of the renin-angiotensin system.
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Angiotensin II Overstimulation Leads to an Increased Susceptibility to Dilated Cardiomyopathy and Higher Mortality in Female Mice
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It is suggested that females are more susceptible to the adverse effects of AT1R stimulation than males favouring the development of HF and increased mortality, and may have more severe eccentric hypertrophy, dysfunction and compromised Ca2+ dynamics.
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It is suggested that Rgs5 is an important regulator of arrhythmogenesis in the mouse atrium and that the enhanced susceptibility to atrial tachyarrhythmias in RGS5−/− mice may contribute to abnormalities of atrial repolarization.
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