Involvement of the brain (pro)renin receptor in cardiovascular homeostasis.
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.
Shan
Zhiying
Z
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Shi
Peng
P
Cuadra
Adolfo E
AE
Dong
Ying
Y
Lamont
Gwyneth J
GJ
Li
Qiuhong
Q
Seth
Dale M
DM
Navar
L Gabriel
LG
Katovich
Michael J
MJ
Sumners
Colin
C
Raizada
Mohan K
MK
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
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins; D000093342:Prorenin Receptor