The compensatory renin-angiotensin system in the central regulation of arterial pressure: New avenues and new challenges

摘要

Hypertension is a widespread condition that affects millions of people around the world and has a great impact in public health. The classic Renin Angiotensin System is a complex system comprised of multiple peptides and pathways that have been the motive of great drug development over the years to control hypertension. However, there are still patients whose hypertension is very difficult to control with the current drugs and strategies, thus motivating further research in this field. In the last two decades, important discoveries have expanded our knowledge of this system and new pathways are emerging that are helping us understand the complex interaction taking place not only in the periphery but also in the central nervous system where the renin angiotensin system is also very active. A new arm, called the ACE2/Ang-(1-7)/Mas receptor axis was shown to exert anti-hypertensive properties and serve as a counterbalance to the classic ACE/Angiotensin-II/AT1 receptor axis; in this way, modulating or even counteracting the negative effects of Angiotensin-II in blood pressure regulation and water retention. Modulation of this new axis through ACE2 activation, ADAM17 regulation or AT1 receptor internalization are some of the novel avenues and challenges that have the potential to become target for new drug research and development for the treatment of hypertension.