Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling
1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. Angiotensin AT1 receptor antagonism has been considered as a specific approach to block the renin–angiotensin system and been demonstrated to be able to prevent or regress LVH by interfering with the remodelling process of the heart.
2. Angiotensin AT1 receptor blockade induces a marked increase in angiotensin (Ang) II, which may stimulate the AT2 receptors. Gene expression of AT1 and AT2 receptors increases in a time-dependent manner in cardiac remodelling following myocardial infarction.
3. Considerable efforts have been made to clarify the role of AT2 receptors in cardiac hypertrophy and remodelling since the mid-1990s, resulting in controversial reports: the AT2 receptor mediates actions either opposite to or in coordination with those of the AT1 receptor. Moreover, there are many reports of no significant effects mediated by AT2 receptors.
4. Based on the studies reviewed in the present article, we assume that the predominant effect of AngII in cardiac hypertrophy and cardiac remodelling is growth promoting and that this effect is mediated mainly via AT1 receptors. The AT2 receptors may affect the hypertrophic process by interacting with other cardiac membrane proteins, enzymes and autacoids. Before coming to a conclusion as to whether AT2 receptor stimulation or antagonism is beneficial to the heart, more studies should be performed in different LVH models, especially long-term treatment protocols in vivo.
Document Type: Research Article
Affiliations: 1: Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of The Ministry of Education, Fudan University Shanghai Medical College, Shanghai, PR China and 2: Department of Pharmacology, National University of Singapore, Singapore
Publication date: December 1, 2003