title: Involvement of the brain (pro)renin receptor in cardiovascular homeostasis.
abstract: BACKGROUND
  Despite overwhelming evidence of the importance of brain renin-angiotensin system (RAS), the very existence of intrinsic brain RAS remains controversial.
  
  
  OBJECTIVE
  To investigate the hypothesis that the brain (pro)renin receptor (PRR) is physiologically important in the brain RAS regulation and cardiovascular functions.
  
  
  RESULTS
  PRR is broadly distributed within neurons of cardiovascular-relevant brain regions. The physiological functions of PRR were studied in the supraoptic nucleus (SON) because this brain region showed greater levels of PRR mRNA in the spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. Adeno-associated virus (AAV)-mediated overexpression of human PRR in the SON of normal rats resulted in increases in plasma and urine vasopressin, and decreases in H(2)O intake and urine output without any effects on mean arterial pressure and heart rate. Knockdown of endogenous PRR by AAV-short hairpin RNA in the SON of SHRs attenuated age-dependent increases in mean arterial pressure and caused a decrease in heart rate and plasma vasopressin. Incubation of neuronal cells in culture with human prorenin and angiotensinogen resulted in increased generation of angiotensin I and II. Furthermore, renin treatment increased phosphorylation of extracellular signal-regulated kinase ½ in neurons from both WKY rats and SHRs; however, the stimulation was 50% greater in the SHR.
  
  
  CONCLUSIONS
  The study demonstrates that brain PRR is functional and plays a role in the neural control of cardiovascular functions. This may help resolve a long-held controversy concerning the existence of intrinsic and functional brain RAS.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Shan
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
authors.forename: Adolfo E
authors.initials: AE
authors.lastname: Cuadra
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Gwyneth J
authors.initials: GJ
authors.lastname: Lamont
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Li
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002319:Cardiovascular System / Q000294:innervation*; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000502:physiology*; D000093342:Prorenin Receptor
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins; D000093342:Prorenin Receptor