title: Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An Update.
abstract: The renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension. Recent studies have also begun to unravel the molecular mechanisms that govern intrarenal RAS activity. This local system is under the control of complex regulatory networks consisting of positive regulators of (pro)renin receptor, Wnt/β-catenin signaling, and PGE2/PGE2receptor EP4subtype, and negative regulators of Klotho, vitamin D receptor, and liver X receptors. This review highlights recent advances in defining the regulation and function of intrarenal RAS as a unique entity separate from systemic angiotensin II generation.
authors.affiliation: Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and Tianxin.Yang@hsc.utah.edu.|Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000502:physiology*
keywords: (pro)renin receptor; Klotho; intrarenal renin-angiotensin system; prostaglandin E4 receptors; β-catenin