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Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Publication ,  Journal Article
Sparks, MA; Rianto, F; Diaz, E; Revoori, R; Hoang, T; Bouknight, L; Stegbauer, J; Vivekanandan-Giri, A; Ruiz, P; Pennathur, S; Abraham, DM ...
Published in: Hypertension
February 2021

Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II in the heart, above and beyond their effects to reduce pressure overload. We generated 2 distinct mouse lines with cell-specific deletion of AT1A receptors, from cardiomyocytes. In the first line (C-SMKO), elimination of AT1A receptors was achieved using a heterologous Cre recombinase transgene under control of the Sm22 promoter, which expresses in cells of smooth muscle lineage including cardiomyocytes and vascular smooth muscle cells of conduit but not resistance vessels. The second line (R-SMKO) utilized a Cre transgene knocked-in to the Sm22 locus, which drives expression in cardiac myocytes and vascular smooth muscle cells in both conduit and resistance arteries. Thus, although both groups lack AT1 receptors in the cardiomyocytes, they are distinguished by presence (C-SMKO) or absence (R-SMKO) of peripheral vascular responses to Ang II. Similar to wild-types, chronic Ang II infusion caused hypertension and cardiac hypertrophy in C-SMKO mice, whereas both hypertension and cardiac hypertrophy were reduced in R-SMKOs. Thus, despite the absence of AT1A receptors in cardiomyocytes, C-SMKOs develop robust cardiac hypertrophy. By contrast, R-SMKOs developed identical levels of hypertrophy in response to pressure overload-induced by transverse aortic banding. Our findings suggest that direct activation of AT1 receptors in cardiac myocytes has minimal influence on cardiac hypertrophy induced by renin-Ang system activation or pressure overload.

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2021

Volume

77

Issue

2

Start / End Page

393 / 404

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Renin-Angiotensin System
  • Receptor, Angiotensin, Type 1
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Hypertension
  • Cardiovascular System & Hematology
 

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Sparks, M. A., Rianto, F., Diaz, E., Revoori, R., Hoang, T., Bouknight, L., … Coffman, T. M. (2021). Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy. Hypertension, 77(2), 393–404. https://doi.org/10.1161/HYPERTENSIONAHA.119.14079
Sparks, Matthew A., Fitra Rianto, Edward Diaz, Ritika Revoori, Thien Hoang, Lucas Bouknight, Johannes Stegbauer, et al. “Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.Hypertension 77, no. 2 (February 2021): 393–404. https://doi.org/10.1161/HYPERTENSIONAHA.119.14079.
Sparks MA, Rianto F, Diaz E, Revoori R, Hoang T, Bouknight L, et al. Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy. Hypertension. 2021 Feb;77(2):393–404.
Sparks, Matthew A., et al. “Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.Hypertension, vol. 77, no. 2, Feb. 2021, pp. 393–404. Pubmed, doi:10.1161/HYPERTENSIONAHA.119.14079.
Sparks MA, Rianto F, Diaz E, Revoori R, Hoang T, Bouknight L, Stegbauer J, Vivekanandan-Giri A, Ruiz P, Pennathur S, Abraham DM, Gurley SB, Crowley SD, Coffman TM. Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy. Hypertension. 2021 Feb;77(2):393–404.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2021

Volume

77

Issue

2

Start / End Page

393 / 404

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Renin-Angiotensin System
  • Receptor, Angiotensin, Type 1
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Hypertension
  • Cardiovascular System & Hematology