AT(2) Receptor and Tissue Injury: Therapeutic Implications

The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT(1) receptor (AT(1)R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well established. In the past twenty years, protective actions of the RAS, not only in the cardiovascular, but also in the nervous system, have been demonstrated. The so-called protective arm of the RAS includes AT(2)-receptors and Mas receptors (AT(2)R and MasR) and is characterized by effects different from and often opposing those of the AT(1)R. These include anti-inflammation, anti-fibrosis, anti-apoptosis and neuroregeneration that can counterbalance pathological processes and enable recovery from disease. The recent development of novel, small-molecule AT(2)R agonists offers a therapeutic potential in humans with a variety of clinical indications.