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Angiotensin II and the vascular phenotype in hypertension

Published online by Cambridge University Press:  30 March 2011

Carmine Savoia
Affiliation:
Clinical and Molecular Medicine Department, Sapienza University of Rome, Cardiology Unit, Sant'Andrea Hospital, Rome, Italy.
Dylan Burger
Affiliation:
Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
Nobu Nishigaki
Affiliation:
Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
Augusto Montezano
Affiliation:
Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
Rhian M. Touyz*
Affiliation:
Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
*
*Corresponding author: Rhian M. Touyz, OHRI/University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. E-mail: rtouyz@uottawa.ca

Abstract

Hypertension is associated with vascular changes characterised by remodelling, endothelial dysfunction and hyperreactivity. Cellular processes underlying these perturbations include altered vascular smooth muscle cell growth and apoptosis, fibrosis, hypercontractility and calcification. Inflammation, associated with macrophage infiltration and increased expression of redox-sensitive pro-inflammatory genes, also contributes to vascular remodelling. Many of these features occur with ageing, and the vascular phenotype in hypertension is considered a phenomenon of ‘premature vascular ageing’. Among the many factors involved in the hypertensive vascular phenotype, angiotensin II (Ang II) is especially important. Ang II, previously thought to be the sole effector of the renin–angiotensin system (RAS), is converted to smaller peptides [Ang III, Ang IV, Ang-(1-7)] that are biologically active in the vascular system. Another new component of the RAS is the (pro)renin receptor, which signals through Ang-II-independent mechanisms and might influence vascular function. Ang II mediates effects through complex signalling pathways on binding to its G-protein-coupled receptors (GPCRs) AT1R and AT2R. These receptors are regulated by the GPCR-interacting proteins ATRAP, ARAP1 and ATIP. AT1R activation induces effects through the phospholipase C pathway, mitogen-activated protein kinases, tyrosine kinases/phosphatases, RhoA/Rhokinase and NAD(P)H-oxidase-derived reactive oxygen species. Here we focus on recent developments and new research trends related to Ang II and the RAS and involvement in the hypertensive vascular phenotype.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

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Briones, A.M. and Touyz, R.M. (2010) Oxidative stress and hypertension: current concepts. Current Hypertension Reports 12, 135-142CrossRefGoogle ScholarPubMed
Wong, W.T. et al. (2010) Endothelial dysfunction: the common consequence in diabetes and hypertension. Journal of Cardiovascular Pharmacology 55, 300-307CrossRefGoogle ScholarPubMed
Nguyen Dinh Cat, A. et al. (2010) The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. FASEB Journal 24, 2454-2463Google ScholarPubMed
Nádasy, G.L. (2010) Biomechanics of resistance artery wall remodeling in angiotensin-II hypertension and subsequent recovery. Kidney Blood Pressure Research 33, 37-47CrossRefGoogle ScholarPubMed
Li, H. et al. (2010) Calmodulin kinase II is required for angiotensin II-mediated vascular smooth muscle hypertrophy. American Journal of Physiology 298, H688-H698Google ScholarPubMed