Angiotensin II and the vascular phenotype in hypertension

Savoia, C.,, Burger, D., Nishigaki, N., Montezano, A. and Touyz, R.M. (2011) Angiotensin II and the vascular phenotype in hypertension. Expert Reviews in Molecular Medicine, 13(e11), pp. 1-25. (doi: 10.1017/S1462399411001815)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Montezano, Dr Augusto and Touyz, Professor Rhian
• Authors: Savoia, C.,, Burger, D., Nishigaki, N., Montezano, A., and Touyz, R.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Expert Reviews in Molecular Medicine
• ISSN (Online): 1462-3994
• Published Online: 30 April 2011