title: A current view of brain renin-angiotensin system: Is the (pro)renin receptor the missing link?
abstract: The renin-angiotensin system (RAS) plays a central role in the brain to regulate blood pressure (BP). This role includes the modulation of sympathetic nerve activity (SNA) that regulates vascular tone; the regulation of secretion of neurohormones that have a critical role in electrolyte as well as fluid homeostasis; and by influencing behavioral processes to increase salt and water intake. Based on decades of research it is clear that angiotensin II (Ang II), the major bioactive product of the RAS, mediates these actions largely via its Ang II type 1 receptor (AT1R), located within hypothalamic and brainstem control centers. However, the mechanisms of brain RAS function have been questioned, due in large part to low expression levels of the rate limiting enzyme renin within the central nervous system. Tissue localized RAS has been observed in heart, kidney tubules and vascular cells. Studies have also given rise to the hypothesis for localized RAS function within the brain, so that Ang II can act in a paracrine manner to influence neuronal activity. The recently discovered (pro)renin receptor (PRR) may be key in this mechanism as it serves to sequester renin and prorenin for localized RAS activity. Thus, the PRR can potentially mitigate the low levels of renin expression in the brain to propagate Ang II action. In this review we examine the regulation, expression and functional properties of the various RAS components in the brain with particular focus on the different roles that PRR may have in BP regulation and hypertension.
authors.affiliation: University of Florida College of Medicine, Department of Physiology and Functional Genomics, 100274 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Adolfo E
authors.initials: AE
authors.lastname: Cuadra
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Shan
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D000093342:Prorenin Receptor
chemical_list: D000959:Antihypertensive Agents; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin; D000093342:Prorenin Receptor