Revised: July 7, 2014
Accepted: July 25, 2014
Published online: August 6, 2014
The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin II(Ang II) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang IIformation or even active Ang II-derived peptides have now been described acting on Ang II AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang II formation. This in situ formation, especially in the kidney, increases Ang II levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang II effects, improves the development of new drugs for treating hypertension and cardiovascular diseases.
Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin II (Ang II)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang II synthesis, new Ang II metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/Mas axis, which presents opposite effects of AT1 activation by Ang II.