title: Epochs in the depressor/pressor balance of the renin-angiotensin system.
abstract: The renin-angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang(1-7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Katrina M Mirabito
authors.initials: KM
authors.lastname: Colafella
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Lucinda M
authors.initials: LM
authors.lastname: Hilliard
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Victoria 3800, Australia kate.denton@monash.edu.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012727:Sex Characteristics; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014662:Vasoconstrictor Agents; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: aging; angiotensin receptors; cardiovascular disease; hypertension; sex differences