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

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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.


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

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Hypertension (Dallas, Tex. : 1979)







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