Angiotensin II and the vascular phenotype in hypertension

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.

Enhanced Angiotensin II-Induced Cardiac and Aortic Remodeling in ACE2 Knockout Mice

“…Ang II induced vascular smooth muscle growth, arterial remodeling and inflammation associated with cellular growth and calcification is well documented (Cheng et al, 2011;Touyz, 2005;Touyz, 2004;Savoia, Burger, Nishigaki, Montezano, & Touyz, 2011). It is reasonable that the presence of ACE2 in the vascular endothelial cell and arterial smooth muscle cells (Donoghue et al, 2000;Hamming et al, 2004) could function protectively in those vessels from the hypertrophic effect of Ang II (Hayashi et al, 2010;Jin, Lu, & Lin, 2011).…”

Progenitor Cells, Bone Marrow–Derived Fibrocytes and Endothelial-to-Mesenchymal Transition

“…Vascular fibrosis of small and large arteries contributes to arterial remodeling, important in the development and complications of hypertension. 1 Fibrogenesis is an active process that involves accumulation of structural proteins (collagen and fibronectin) and adhesion proteins (laminin and fibronectin), expression of adhesion molecules and integrins, and remodeling of the ECM. 2 Healthy arteries are surrounded by perivascular adventitial tissue comprising collagens I and III in the intima, media, and adventitia, with collagen types I, III, IV, and V in the endothelial and vascular smooth muscle cell basement membranes.…”

Impact of the Direct Angiotensin II Type 2 Receptor Stimulation on Renal Function

“…Although the mechanisms underlying these sex differences remain unclear, divergences in the function of the reninangiotensin system (RAS) and differences in the response to stimulation and inhibition of RAS in men and premenopausal women have been proposed. 1,2 RAS is involved in blood pressure regulation by modulating vascular tone and renal excretory function. In particular, the kidney is involved in the long-term regulation of arterial pressure by modulating sodium excretion.…”

“…In particular, the kidney is involved in the long-term regulation of arterial pressure by modulating sodium excretion. 1 It is now generally accepted that RAS organization is dual and that beside the well-known main pressor axis (angiotensin-converting enzyme/angiotensin [Ang] II/Ang type 1 receptor [AT1R]), there is a second depressor protective axis consisting of Ang type 2 receptor (AT2R), angiotensin-converting enzyme 2, Ang-(1-7), and MasR. 1 In particular, AT2R mediates the vasodilatory and natriuretic actions of angiotensin peptides.…”

“…1 It is now generally accepted that RAS organization is dual and that beside the well-known main pressor axis (angiotensin-converting enzyme/angiotensin [Ang] II/Ang type 1 receptor [AT1R]), there is a second depressor protective axis consisting of Ang type 2 receptor (AT2R), angiotensin-converting enzyme 2, Ang-(1-7), and MasR. 1 In particular, AT2R mediates the vasodilatory and natriuretic actions of angiotensin peptides. AT2R is expressed throughout the kidney in both vascular and tubular elements, and it is greatly expressed in renal proximal tubule cells.…”