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Redox‐dependent signalling by angiotensin II and vascular remodelling in hypertension
Author(s) -
Touyz Rhian M,
Tabet Fatiha,
Schiffrin Ernesto L
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03930.x
Subject(s) - vascular remodelling in the embryo , angiotensin ii , vascular smooth muscle , microbiology and biotechnology , second messenger system , signal transduction , angiotensin ii receptor type 1 , protein tyrosine phosphatase , nadph oxidase , medicine , biology , protein kinase a , downregulation and upregulation , endocrinology , reactive oxygen species , chemistry , kinase , receptor , biochemistry , smooth muscle , gene
Summary 1. Hypertension is associated with structural alterations of resistance arteries, a process known as remodelling (increased media‐to‐lumen ratio). 2. At the cellular level, vascular remodelling involves changes in vascular smooth muscle cell (VSMC) growth, cell migration, inflammation and fibrosis. These processes are mediated via multiple factors, of which angiotensin (Ang) II appears to be one of the most important in hypertension. 3. Angiotensin II signalling, via AT 1 receptors, is upregulated in VSMC from resistance arteries of hypertensive patients and rats. This is associated with hyperactivation of vascular NADPH oxidase, leading to increased generation of reactive oxygen species (ROS), particularly O 2 – and H 2 O 2 . 4. Reactive oxygen species function as important intracellular second messengers to activate many downstream signalling molecules, such as mitogen‐activated protein kinase, protein tyrosine phosphatases, protein tyrosine kinases and transcription factors. Activation of these signalling cascades leads to VSMC growth and migration, modulation of endothelial function, expression of pro‐inflammatory mediators and modification of extracellular matrix. 5. Furthermore, ROS increase intracellular free Ca 2+ concentration ([Ca 2+ ] i ), a major determinant of vascular reactivity. 6. All these processes play major roles in vascular injury associated with hypertension. Accordingly, ROS and the signalling pathways that they modulate provide new targets to regress vascular remodelling, reduce peripheral resistance and prevent hypertensive end‐organ damage. 7. In the present review, we discuss the role of ROS as second messengers in AngII signalling and focus on the implications of these events in the processes underlying vascular remodelling in hypertension.