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

Authors

Keisuke Okuno, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).
Keiichi Torimoto, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).
Stephanie M. Cicalese, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).
Kyle Preston, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).
Victor Rizzo, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).
Tomoki Hashimoto, Barrow Aneurysm and AVM Research Center, Departments of Neurosurgery and Neurobiology, Barrow Neurological Institute, Phoenix, AZ (T.H.).Follow
Thomas M. Coffman, Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, NC (T.M.C., M.A.S.).
Matthew A. Sparks, Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, NC (T.M.C., M.A.S.).
Satoru Eguchi, Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., K.T., S.M.C., K.P., V.R., S.E.).

Document Type

Article

Abstract

BACKGROUND: Ang II (angiotensin II) type 1 (AT) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT receptor (AT and AT) of which knock-in -mediated smooth muscle AT 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 AT in this process remains unexplored. Accordingly, it is hypothesized that smooth muscle AT 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 AT receptor silenced mice, knock-in -mediated constitutive smooth muscle AT receptor silenced mice, and -mediated inducible smooth muscle AT together with global AT 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 AT receptor silenced mice. Coronary arterial perivascular fibrosis in response to Ang II infusion was also attenuated in both AT receptor silenced mice. Ang II-induced cardiac hypertrophy was attenuated in constitutive smooth muscle AT receptor silenced mice. However, Ang II-induced cardiac hypertrophy and hypertension were not altered in inducible smooth muscle AT receptor silenced mice. CONCLUSIONS: Smooth muscle AT 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.

Keywords

angiotensin II, fibrosis, hypertension, receptor, vascular smooth muscle cell

Medical Subject Headings

Mice; Animals; Receptor, Angiotensin, Type 1 (genetics); Angiotensin II (pharmacology); Vascular Remodeling; Hypertension; Myocytes, Smooth Muscle; Cardiomegaly; Fibrosis; Mice, Knockout; Mice, Inbred C57BL

Publication Date

3-1-2023

Publication Title

Hypertension (Dallas, Tex. : 1979)

E-ISSN

1524-4563

Volume

80

Issue

3

First Page

668

Last Page

677

PubMed ID

36628961

Digital Object Identifier (DOI)

10.1161/HYPERTENSIONAHA.122.20601

Recommended Citation

Okuno, Keisuke; Torimoto, Keiichi; Cicalese, Stephanie M.; Preston, Kyle; Rizzo, Victor; Hashimoto, Tomoki; Coffman, Thomas M.; Sparks, Matthew A.; and Eguchi, Satoru, "Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II" (2023). Translational Neuroscience. 2235.
https://scholar.barrowneuro.org/neurobiology/2235