Received April 1, 2005
Revised April 21, 2005
Accepted after revision May 10, 2005
Intracellular Mechanisms Involved in Vascular Remodeling of Resistance Arteries in Hypertension: Role of Angiotensin II
Rhian M Touyz 1*
1 University of Ottawa
* To whom correspondence should be addressed. E-mail: touyzr{at}ircm.qc.ca.
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Abstract |
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Resistance arteries undergo structural changes (vascular remodeling) in hypertension. These changes involve media thickening, reduced lumen diameter and consequent increased media:lumen ratio. Cellular processes underlying these events include altered vascular smooth muscle cell (VSMC) growth, migration, differentiation and increased extracellular matrix abundance. Another factor contributing to remodeling is inflammation, associated with macrophage infiltration, fibrosis and increased expression of redox-sensitive pro-inflammatory genes. Among the factors involved in arterial remodeling, Ang II appears to be one of the most important. Ang II, a multifunctional peptide with pleiotropic actions modulates vasomotor tone, cell growth, apoptosis/anoikis, cell migration and extracellular matrix deposition. It is proinflammatory and it stimulates production of growth factors and vasoactive agents. The multiple actions of Ang II are mediated via complex intracellular signaling pathways including stimulation of the PLC-IP3-DAG cascade, MAP kinases, tyrosine kinases and RhoA/Rho kinase. Furthermore, Ang II elicits many of its (patho)physiological effects by stimulating reactive oxygen species (•O2- and H2O2) generation through activation of vascular NAD(P)H oxidase. •O2- and H2O2 in turn influence downstream signaling molecules including transcription factors, tyrosine kinases/phosphatases, Ca2+ channels and MAP kinases. Interaction between these systems is complex and dysregulation at any level may contribute to vascular remodeling. Targeting such molecules/pathways could prevent or regress hypertensive vascular damage thereby ameliorating development of hypertension and preventing target organ damage. The present review discusses the role of Ang II in remodeling of resistance arteries, focusing on some signaling pathways involved in vascular growth and inflammation in hypertension.
Key Words:
Angiotensin, Hypertension, Intracellular signalling
