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Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts.

Publication ,  Journal Article
van Esch, JHM; Gembardt, F; Sterner-Kock, A; Heringer-Walther, S; Le, TH; Lassner, D; Stijnen, T; Coffman, TM; Schultheiss, H-P; Danser, AHJ ...
Published in: Cardiovasc Res
June 1, 2010

AIMS: Our aim was to determine the contribution of the three angiotensin (Ang) II receptor subtypes (AT(1a), AT(1b), AT(2)) to coronary responsiveness, cardiac histopathology, and tissue Ang II levels using mice deficient for one, two, or all three Ang II receptors. METHODS AND RESULTS: Hearts of knockout mice and their wild-type controls were collected for histochemistry or perfused according to Langendorff, and kidneys were removed to measure tissue Ang II. Ang II dose-dependently decreased coronary flow (CF) and left ventricular systolic pressure (LVSP), and these effects were absent in all genotypes deficient for AT(1a), independently of AT(1b) and AT(2). The deletion of Ang II receptors had an effect neither on the morphology of medium-sized vessels in the heart nor on the development of fibrosis. However, the lack of both AT(1) subtypes was associated with atrophic changes in the myocardium, a reduced CF and a reduced LVSP. AT(1a) deletion alone, independently of the presence or absence of AT(1b) and/or AT(2), reduced renal Ang II by 50% despite a five-fold rise of plasma Ang II. AT(1b) deletion, on top of AT(1a) deletion (but not alone), further decreased tissue Ang II, while increasing plasma Ang II. In mice deficient for all three Ang II receptors, renal Ang II was located only extracellularly. CONCLUSION: The lack of both AT(1) subtypes led to a baseline reduction of CF and LVSP, and the effects of Ang II on CF and LVSP were found to be exclusively mediated via AT(1a). The lack of AT(1a) or AT(1b) does not influence the development or maintenance of normal cardiac morphology, whereas deficiency for both receptors led to atrophic changes in the heart. Renal Ang II levels largely depend on AT(1) binding of extracellularly generated Ang II, and in the absence of all three Ang II receptors, renal Ang II is only located extracellularly.

Duke Scholars

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

June 1, 2010

Volume

86

Issue

3

Start / End Page

401 / 409

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Pressure
  • Ventricular Function, Left
  • Receptor, Angiotensin, Type 2
  • Receptor, Angiotensin, Type 1
  • Phenotype
  • Perfusion
  • Natriuretic Peptide, Brain
  • Myocardium
  • Mice, Knockout
 

Citation

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van Esch, J. H. M., Gembardt, F., Sterner-Kock, A., Heringer-Walther, S., Le, T. H., Lassner, D., … Walther, T. (2010). Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts. Cardiovasc Res, 86(3), 401–409. https://doi.org/10.1093/cvr/cvq004
Esch, Joep H. M. van, Florian Gembardt, Anja Sterner-Kock, Silvia Heringer-Walther, Thu H. Le, Dirk Lassner, Theo Stijnen, et al. “Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts.Cardiovasc Res 86, no. 3 (June 1, 2010): 401–9. https://doi.org/10.1093/cvr/cvq004.
van Esch JHM, Gembardt F, Sterner-Kock A, Heringer-Walther S, Le TH, Lassner D, et al. Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts. Cardiovasc Res. 2010 Jun 1;86(3):401–9.
van Esch, Joep H. M., et al. “Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts.Cardiovasc Res, vol. 86, no. 3, June 2010, pp. 401–09. Pubmed, doi:10.1093/cvr/cvq004.
van Esch JHM, Gembardt F, Sterner-Kock A, Heringer-Walther S, Le TH, Lassner D, Stijnen T, Coffman TM, Schultheiss H-P, Danser AHJ, Walther T. Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts. Cardiovasc Res. 2010 Jun 1;86(3):401–409.
Journal cover image

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

June 1, 2010

Volume

86

Issue

3

Start / End Page

401 / 409

Location

England

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Pressure
  • Ventricular Function, Left
  • Receptor, Angiotensin, Type 2
  • Receptor, Angiotensin, Type 1
  • Phenotype
  • Perfusion
  • Natriuretic Peptide, Brain
  • Myocardium
  • Mice, Knockout