Renin-angiotensin system: upgrade of recent knowledge and perspectives

Abstract

Although more than 100 years passed from the renin-angiotensin system (RAS) discovery, new knowledge is still ceaselessly accruing in this field. The present review provides brief overview on the history of the RAS investigation, circulating and tissue RAS, and outlines the physiological functions of the RAS major active substance, angiotensin II (ANG II). Circulating ANG II is generated from angiotensin I (ANG I) by carboxypeptidaze angiotensin-converting enzyme (ACE) expressed in the pulmonary endothelial cells. ANG I is formed from angiotensinogen, originating in the liver, by renal peptidase renin secreted by the juxtaglomerular cells. The ANG II effects are mediated mainly via AT1 receptors. Scientific, medical, and pharmacological interests in the RAS relay mainly in its potency to influence the blood pressure and heart hypertrophy. Inhibition of ACE and AT1 receptors has been shown to be very useful in the hypertension management although several unexpected effects of this treatment led to the initiation of new studies. This review also describes other bioactive angiotensins and modifying enzymes identified during the last years, the ways how the RAS activity can be measured and ANG II degraded in the organism. It also indicates the most convenient models for the RAS investigation. Finally, the major mechanisms of the RAS activity regulation are also described. angiotensin, angiotensin-converting enzyme, angiotensin-converting enzyme 2, angiotensin AT1 receptors, experimental model.