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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+Heart+Circ+Physiol
2015 ; 309
(5
): H880-7
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Activation of the (pro)renin receptor in the paraventricular nucleus increases
sympathetic outflow in anesthetized rats
#MMPMID26116710
Huber MJ
; Basu R
; Cecchettini C
; Cuadra AE
; Chen QH
; Shan Z
Am J Physiol Heart Circ Physiol
2015[Sep]; 309
(5
): H880-7
PMID26116710
show ga
Previous studies have indicated that hyperactivity of brain prorenin receptors
(PRR) is implicated in neurogenic hypertension. However, the role of brain PRR in
regulating arterial blood pressure (ABP) is not well understood. Here, we test
the hypothesis that PRR activation in the hypothalamic paraventricular nucleus
(PVN) contributes to increased sympathetic nerve activity (SNA). In anaesthetized
adult Sprague-Dawley (SD) rats, bilateral PVN microinjection of human prorenin (2
pmol/side) significantly increased splanchnic SNA (SSNA; 71 ± 15%, n = 7).
Preinjection of either prorenin handle region peptide, the PRR binding blocker
(PRRB), or tiron (2 nmol/side), the scavenger of reactive oxygen species (ROS),
significantly attenuated the increase in SSNA (PRRB: 32 ± 5% vs. control, n = 6;
tiron: 8 ± 10% vs. control, n = 5; P < 0.05) evoked by prorenin injection. We
further investigated the effects of PRR activation on ROS production as well as
downstream gene expression using cultured hypothalamus neurons from newborn SD
rats. Incubation of brain neurons with human prorenin (100 nM) dramatically
enhanced ROS production and induced a time-dependent increase in mRNA levels of
inducible nitric oxide synthase (iNOS), NAPDH oxidase 2 subunit cybb, and
FOS-like antigen 1 (fosl1), a marker for neuronal activation and a component of
transcription factor activator protein-1 (AP-1). The maximum mRNA increase in
these genes occurred 6 h following incubation (iNOS: 201-fold; cybb: 2 -fold;
Ffosl1: 11-fold). The increases in iNOS and cybb mRNA were not attenuated by the
AT1 receptor antagonist losartan but abolished by the AP-1 blocker curcumin. Our
results suggest that PVN PRR activation induces sympathoexcitation possibly
through stimulation of an ANG II-independent, ROS-AP-1-iNOS signaling pathway.