title: The intrarenal renin-angiotensin system in hypertension.
abstract: The renin-angiotensin system (RAS) is a well-studied hormonal cascade controlling fluid and electrolyte balance and blood pressure through systemic actions. The classical RAS includes renin, an enzyme catalyzing the conversion of angiotensinogen to angiotensin (Ang) I, followed by angiotensin-converting enzyme (ACE) cleavage of Ang I to II, and activation of AT1 receptors, which are responsible for all RAS biologic actions. Recent discoveries have transformed the RAS into a far more complex system with several new pathways: the (des-aspartyl(1))-Ang II (Ang III)/AT2 receptor pathway, the ACE-2/Ang (1-7)/Mas receptor pathway, and the prorenin-renin/prorenin receptor/mitogen-activated protein kinase pathway, among others. Although the classical RAS pathway induces Na(+) reabsorption and increases blood pressure, several new pathways constitute a natriuretic/vasodilator arm of the system, opposing detrimental actions of Ang II through Ang II type 1 receptors. Instead of a simple circulating RAS, several independently functioning tissue RASs exist, the most important of which is the intrarenal RAS. Several physiological characteristics of the intrarenal RAS differ from those of the circulating RAS, autoamplifying the activity of the intrarenal RAS and leading to hypertension. This review will update current knowledge on the RAS with particular attention to the intrarenal RAS and its role in the pathophysiology of hypertension.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA. Electronic address: rmc4c@virginia.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carey
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System; D012964:Sodium / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000803:Angiotensin I; D012964:Sodium; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin; Hypertension; Kidney; Renin; Sodium