title: The compensatory renin-angiotensin system in the central regulation of arterial pressure: new avenues and new challenges.
abstract: Hypertension is a widespread condition that affects millions of people around the world and has a major impact in public health. The classic renin-angiotensin system is a complex system comprised of multiple peptides and pathways that have been the driver of drug development over the years to control hypertension. However, there are still patients whose hypertension is very difficult to control with current drugs and strategies, thus motivating further research in this field. In the past 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 antihypertensive 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 a target for new drug research and development for the treatment of hypertension.
authors: Department of Pharmacology and Experimental Therapeutics, Neurosciences and Cardiovascular Centers of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors: Alberto
authors: A
authors: Mendoza
authors: Louisiana State University Health Sciences Center, School of Medicine, Department of Pharmacology and Experimental Therapeutics, 1901 Perdido St, Rm 5218, New Orleans, LA 70112, USA elazar@lsuhsc.edu.
authors: Eric
authors: E
authors: Lazartigues
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: ACE2; ADAM17; DOCA-salt hypertension; angiotensin II; antioxidant; oxidative stress