PMID- 20689062
OWN - NLM
STAT- MEDLINE
DCOM- 20101022
LR  - 20221207
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 107
IP  - 7
DP  - 2010 Oct 1
TI  - Involvement of the brain (pro)renin receptor in cardiovascular homeostasis.
PG  - 934-8
LID - 10.1161/CIRCRESAHA.110.226977 [doi]
AB  - RATIONALE: 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. METHODS AND 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 (1/2) 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.
FAU - Shan, Zhiying
AU  - Shan Z
AD  - Department of Physiology and Functional Genomics, University of Florida, 
      Gainesville, FL 32610, USA.
FAU - Shi, Peng
AU  - Shi P
FAU - Cuadra, Adolfo E
AU  - Cuadra AE
FAU - Dong, Ying
AU  - Dong Y
FAU - Lamont, Gwyneth J
AU  - Lamont GJ
FAU - Li, Qiuhong
AU  - Li Q
FAU - Seth, Dale M
AU  - Seth DM
FAU - Navar, L Gabriel
AU  - Navar LG
FAU - Katovich, Michael J
AU  - Katovich MJ
FAU - Sumners, Colin
AU  - Sumners C
FAU - Raizada, Mohan K
AU  - Raizada MK
LA  - eng
GR  - P20 RR017659/RR/NCRR NIH HHS/United States
GR  - R01 HL076312/HL/NHLBI NIH HHS/United States
GR  - P20RR-017659/RR/NCRR NIH HHS/United States
GR  - R37 HL033610/HL/NHLBI NIH HHS/United States
GR  - R37 HL33610/HL/NHLBI NIH HHS/United States
GR  - HL76312/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100805
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 0 (Prorenin Receptor)
SB  - IM
MH  - Animals
MH  - Blood Pressure/physiology
MH  - Cardiovascular System/*innervation
MH  - Gene Knockdown Techniques
MH  - Green Fluorescent Proteins/genetics
MH  - Homeostasis/physiology
MH  - Hypertension/physiopathology
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cell Surface/*genetics/*metabolism
MH  - Renin-Angiotensin System/*physiology
MH  - Supraoptic Nucleus/*physiology
MH  - Prorenin Receptor
PMC - PMC2948614
MID - NIHMS229482
EDAT- 2010/08/07 06:00
MHDA- 2010/10/23 06:00
PMCR- 2011/10/01
CRDT- 2010/08/07 06:00
PHST- 2010/08/07 06:00 [entrez]
PHST- 2010/08/07 06:00 [pubmed]
PHST- 2010/10/23 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - CIRCRESAHA.110.226977 [pii]
AID - 10.1161/CIRCRESAHA.110.226977 [doi]
PST - ppublish
SO  - Circ Res. 2010 Oct 1;107(7):934-8. doi: 10.1161/CIRCRESAHA.110.226977. Epub 2010 
      Aug 5.