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Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.

Publication ,  Journal Article
Okuno, K; Torimoto, K; Cicalese, SM; Preston, K; Rizzo, V; Hashimoto, T; Coffman, TM; Sparks, MA; Eguchi, S
Published in: Hypertension
March 2023

BACKGROUND: Ang II (angiotensin II) type 1 (AT1) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT1 receptor (AT1A and AT1B) of which knock-in Tagln-mediated smooth muscle AT1A silencing attenuated Ang II-induced hypertension. Although vascular remodeling, a significant contributor to organ damage, occurs concurrently with hypertension in Ang II-infused mice, the contribution of smooth muscle AT1A in this process remains unexplored. Accordingly, it is hypothesized that smooth muscle AT1A receptors exclusively contribute to both medial thickening and adventitial fibrosis regardless of the presence of hypertension. METHODS: About 1 µg/kg per minute Ang II was infused for 2 weeks in 2 distinct AT1A receptor silenced mice, knock-in Tagln-mediated constitutive smooth muscle AT1A receptor silenced mice, and Myh11-mediated inducible smooth muscle AT1A together with global AT1B silenced mice for evaluation of hypertensive cardiovascular remodeling. RESULTS: Medial thickness, adventitial collagen deposition, and immune cell infiltration in aorta were increased in control mice but not in both smooth muscle AT1A receptor silenced mice. Coronary arterial perivascular fibrosis in response to Ang II infusion was also attenuated in both AT1A receptor silenced mice. Ang II-induced cardiac hypertrophy was attenuated in constitutive smooth muscle AT1A receptor silenced mice. However, Ang II-induced cardiac hypertrophy and hypertension were not altered in inducible smooth muscle AT1A receptor silenced mice. CONCLUSIONS: Smooth muscle AT1A receptors mediate Ang II-induced vascular remodeling including medial hypertrophy and inflammatory perivascular fibrosis regardless of the presence of hypertension. Our data suggest an independent etiology of blood pressure elevation and hypertensive vascular remodeling in response to Ang II.

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

March 2023

Volume

80

Issue

3

Start / End Page

668 / 677

Location

United States

Related Subject Headings

  • Vascular Remodeling
  • Receptor, Angiotensin, Type 1
  • Myocytes, Smooth Muscle
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Hypertension
  • Fibrosis
  • Cardiovascular System & Hematology
  • Cardiomegaly
 

Citation

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Chicago
ICMJE
MLA
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Okuno, K., Torimoto, K., Cicalese, S. M., Preston, K., Rizzo, V., Hashimoto, T., … Eguchi, S. (2023). Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II. Hypertension, 80(3), 668–677. https://doi.org/10.1161/HYPERTENSIONAHA.122.20601
Okuno, Keisuke, Keiichi Torimoto, Stephanie M. Cicalese, Kyle Preston, Victor Rizzo, Tomoki Hashimoto, Thomas M. Coffman, Matthew A. Sparks, and Satoru Eguchi. “Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.Hypertension 80, no. 3 (March 2023): 668–77. https://doi.org/10.1161/HYPERTENSIONAHA.122.20601.
Okuno K, Torimoto K, Cicalese SM, Preston K, Rizzo V, Hashimoto T, et al. Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II. Hypertension. 2023 Mar;80(3):668–77.
Okuno, Keisuke, et al. “Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.Hypertension, vol. 80, no. 3, Mar. 2023, pp. 668–77. Pubmed, doi:10.1161/HYPERTENSIONAHA.122.20601.
Okuno K, Torimoto K, Cicalese SM, Preston K, Rizzo V, Hashimoto T, Coffman TM, Sparks MA, Eguchi S. Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II. Hypertension. 2023 Mar;80(3):668–677.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

March 2023

Volume

80

Issue

3

Start / End Page

668 / 677

Location

United States

Related Subject Headings

  • Vascular Remodeling
  • Receptor, Angiotensin, Type 1
  • Myocytes, Smooth Muscle
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Hypertension
  • Fibrosis
  • Cardiovascular System & Hematology
  • Cardiomegaly