Role of α1D-adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension

Gallardo-Ortíz, I.A., Rodríguez-Hernández, S.N., López-Guerrero, J.J., Del Valle-Mondragón, L., López-Sánchez, P., Touyz, R.M. and Villalobos-Molina, R. (2015) Role of α1D-adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension. Autonomic and Autacoid Pharmacology, 35(3), pp. 17-31. (doi: 10.1111/aap.12035) (PMID:26845248)

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Abstract

The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1-adrenoceptors (α1-ARs) expression was explored. Alzet® minipumps filled with Ang II (200 ng kg−1 min−1) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1R antagonist, or with BMY 7378, a selective α1D-AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased α1D-ARs without modifying the other α1-ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1Rs and α1D-ARs. Angiotensin II-induced α1D-AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a α1D-AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Gallardo-Ortíz, I.A., Rodríguez-Hernández, S.N., López-Guerrero, J.J., Del Valle-Mondragón, L., López-Sánchez, P., Touyz, R.M., and Villalobos-Molina, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Autonomic and Autacoid Pharmacology
Publisher:Wiley
ISSN:1474-8665
ISSN (Online):1474-8673
Published Online:04 February 2016

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