Pathophysiological Role of Angiotensin II Type 2 Receptor in Cardiovascular and Renal Diseases
- 14 December 1998
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 83 (12), 1182-1191
- https://doi.org/10.1161/01.res.83.12.1182
Abstract
—Since the discovery of nonpeptidic ligands, the receptors for angiotensin (Ang) II have been classified into 2 subtypes (Ang II type 1 receptor [AT1-R] and Ang II type 2 receptor [AT2-R]). AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus. Its expression is very low in the cardiovascular system of the adult. The expression of AT2-R can be modulated by pathological states associated with tissue remodeling or inflammation. In failing hearts or neointima formation after vascular injury, AT2-R is reexpressed in cells proliferating in interstitial regions or neointima and exerts an inhibitory effect on Ang II-induced mitogen signals or synthesis of extracellular matrix proteins, resulting in attenuation of the tissue remodeling. An extreme form of cell growth inhibition ends in programmed cell death, and this process, which is initiated by the withdrawal of growth factors, is also enhanced by AT2-R. Cardiac myocyte- or vascular smooth muscle–specific mice that overexpress AT2-R display an inhibition of Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells and the maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal systems, resulting in AT2-R–mediated cardioprotection, vasodilation, and pressure natriuresis. These effects, transmitted by AT2-R, are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi protein–dependent manner. The expression level of AT2-R is much higher in human hearts than in rodent hearts, and the AT2-R–mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists. Thus, in this review, the regulation of AT2-R expression, its cellular localization, its pathological role in cardiovascular and kidney diseases, and pharmacotherapeutic effects of AT2-R stimulation are discussed.Keywords
This publication has 90 references indexed in Scilit:
- Inhibition of Cell Proliferation and Activation of Protein Tyrosine Phosphatase Mediated by Angiotensin II Type 2 (AT2) Receptor in R3T3 CellsBiochemical and Biophysical Research Communications, 1996
- Gene Transcription of Angiotensin II Type 2 Receptor Is Repressed by Growth Factors and Glucocorticoids in PC12 CellsBiochemical and Biophysical Research Communications, 1995
- Characterization of Angiotensin II Receptor Type 2 during Differentiation and Apoptosis of Rat Ovarian Cultured Granulosa CellsBiochemical and Biophysical Research Communications, 1995
- Molecular Cloning of the Human Angiotensin II Type 2 Receptor cDNABiochemical and Biophysical Research Communications, 1994
- Human Cardiac Fibroblasts Express an Angiotensin Receptor with Unusual Binding Characteristics Which Is Coupled to Cellular ProliferationBiochemical and Biophysical Research Communications, 1994
- Human Type 2 Angiotensin II Receptor Gene: Cloned, Mapped to the X Chromosome, and Its mRNA Is Expressed in the Human LungBiochemical and Biophysical Research Communications, 1994
- Molecular Cloning and Expression of the Gene Encoding Human Angiotensin II Type 2 ReceptorBiochemical and Biophysical Research Communications, 1994
- Novel Subtype of Human Angiotensin II Type 1 Receptor: cDNA Cloning and ExpressionBiochemical and Biophysical Research Communications, 1994
- The angiotensin AT2 receptor stimulates protein tyrosine phosphatase activity and mediates inhibition of particulate guanylate cyclaseBiochemical and Biophysical Research Communications, 1992
- Angiotensin receptor subtypes in rat, rabbit and monkey tissues: Relative distribution and species dependencyLife Sciences, 1991