Brain Cytosolic Phospholipase A2? Mediates Angiotensin II-Induced Hypertension and Reactive Oxygen Species Production in Male Mice.

ABSTRACT: 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.

SUBMITTER: Song CY 

PROVIDER: S-EPMC5905655 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature