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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+Hypertens
2018 ; 31
(5
): 622-629
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Brain Cytosolic Phospholipase A2? Mediates Angiotensin II-Induced Hypertension
and Reactive Oxygen Species Production in Male Mice
#MMPMID29342227
Song CY
; Khan NS
; Liao FF
; Wang B
; Shin JS
; Bonventre JV
; Malik KU
Am J Hypertens
2018[Apr]; 31
(5
): 622-629
PMID29342227
show ga
BACKGROUND: Recently, we reported that angiotensin II (Ang II)-induced
hypertension is mediated by group IV cytosolic phospholipase A2? (cPLA2?) via
production of prohypertensive eicosanoids. Since Ang II increases blood pressure
(BP) via its action in the subfornical organ (SFO), it led us to investigate the
expression and possible contribution of cPLA2? to oxidative stress and
development of hypertension in this brain area. METHODS: Adenovirus (Ad)-green
fluorescence protein (GFP) cPLA2? short hairpin (sh) RNA (Ad-cPLA2? shRNA) and
its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence
protein cPLA2? DNA (Ad-cPLA2? DNA) and its control Ad-GFP DNA were transduced
into SFO of cPLA2?+/+ and cPLA2?-/- male mice, respectively. Ang II (700
ng/kg/min) was infused for 14 days in these mice, and BP was measured by
tail-cuff and radio telemetry. cPLA2 activity, reactive oxygen species
production, and endoplasmic reticulum stress were measured in the SFO. RESULTS:
Transduction of SFO with Ad-cPLA2? shRNA, but not Ad-Scr shRNA in cPLA2?+/+ mice,
minimized expression of cPLA2?, Ang II-induced cPLA2? activity and oxidative
stress in the SFO, BP, and cardiac and renal fibrosis. In contrast, Ad-cPLA2?
DNA, but not its control Ad-GFP DNA in cPLA2?-/- mice, restored the expression of
cPLA2?, and Ang II-induced increase in cPLA2 activity and oxidative stress in the
SFO, BP, cardiac, and renal fibrosis. CONCLUSIONS: These data suggest that cPLA2?
in the SFO is crucial in mediating Ang II-induced hypertension and associated
pathogenesis. Therefore, development of selective cPLA2? inhibitors could be
useful in treating hypertension and its pathogenesis.
|Angiotensin II/*pharmacology
[MESH]
|Animals
[MESH]
|Brain/*enzymology
[MESH]
|Collagen/metabolism
[MESH]
|Endoplasmic Reticulum Stress
[MESH]
|Group IV Phospholipases A2/antagonists & inhibitors/genetics/*physiology
[MESH]