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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2014 ; 307
(8
): F949-61
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Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the
proximal tubule of the kidney
#MMPMID25164083
Li XC
; Gu V
; Miguel-Qin E
; Zhuo JL
Am J Physiol Renal Physiol
2014[Oct]; 307
(8
): F949-61
PMID25164083
show ga
Caveolin 1 (CAV-1) functions not only as a constitutive scaffolding protein of
caveolae but also as a vesicular transporter and signaling regulator. In the
present study, we tested the hypothesis that CAV-1 knockout (CAV-1 KO) inhibits
ANG II type 1 [AT1 (AT1a)] receptor-mediated uptake of ANG II in the proximal
tubule and attenuates blood pressure responses in ANG II-induced hypertension. To
determine the role of CAV-1 in mediating the uptake of FITC-labeled ANG II,
wild-type (WT) mouse proximal convoluted tubule cells were transfected with CAV-1
small interfering (si)RNA for 48 h before AT1 receptor-mediated uptake of
FITC-labeled ANG II was studied. CAV-1 siRNA knocked down CAV-1 expression by
>90% (P < 0.01) and inhibited FITC-labeled ANG II uptake by >50% (P < 0.01).
Moreover, CAV-1 siRNA attenuated ANG II-induced activation of MAPK ERK1/2 and
Na(+)/H(+) exchanger 3 expression, respectively (P < 0.01). To determine whether
CAV-1 regulates ANG II uptake in the proximal tubule, Alexa 488-labeled ANG II
was infused into anesthetized WT and CAV-1 KO mice for 60 min (20 ng/min iv).
Imaging analysis revealed that Alexa 488-labeled ANG II uptake was decreased by
>50% in CAV-1 KO mice (P < 0.01). Furthermore, Val(5)-ANG II was infused into WT
and CAV-1 KO mice for 2 wk (1.5 mg·kg(-1)·day(-1) ip). Basal systolic pressure
was higher, whereas blood pressure and renal excretory and signaling responses to
ANG II were attenuated, in CAV-1 KO mice (P < 0.01). We concluded that CAV-1
plays an important role in AT1 receptor-mediated uptake of ANG II in the proximal
tubule and modulates blood pressure and renal responses to ANG II.