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ACE2 Dose Dependently Inhibits Oxidative Stress In The Brain Of Renovascular Hypertensive Mice
Author(s) -
Xia Huijing,
Lazartigues Eric
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.846.9
The effects of brain ACE2 overexpression on hypertension‐induced oxidative stress were studied using transgenic mice with modest (MA) and high (HA) levels of ACE2. Renovascular hypertension in MA, HA and wildtype (WT) mice (n=5) was induced by 2K1C surgery and blood pressure (BP) monitored by telemetry. Superoxide level was measured in the RVLM using DHE staining (Arbitrary units: AU). NADPH oxidase (NOX) and superoxide dismutase (SOD) activity (U/mg) were assessed in hypothalamus (HT) and brainstem (BS). Four weeks after 2K1C surgery, the hypertension observed in WT mice (Mean BP: 124±14 mmHg) was slightly attenuated by modest ACE2 expression (117±6 mmHg) but completely prevented by high ACE2 expression (106±3 mmHg, P <0.05), while DHE staining was significantly reduced only in HA (3.0±0.3, P <0.05) compared to WT hypertensive mice (3.9±0.3). NOX activity was slightly decreased in MA in both HT (1215±87, P =0.06) and BS (973±79, P =0.056), and significantly reduced in HA (HT: 1135±39, BS: 703±17, P <0.05), compared to WT mice (HT: 1394±38, BS: 1185±56). SOD activity was significantly increased only in HA (HT: 52±5 vs. 38±4, BS: 59±3 vs. 50±2, P <0.05 vs. WT) mice. Our data suggest that ACE2 over‐expression “dose‐dependently” decreases oxidative stress in the RVLM by activating SOD and inhibiting NOX, thus contributing to the prevention of renovascular hypertension. (HL093178 and APS Postdoctoral Fellowship)