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Endothelial Cell TRPA1 Channel Activity Delays the Onset of Hypertension‐Associated Hemorrhagic Stroke
Author(s) -
Sullivan Michelle,
Robinson Jennifer,
Li Wencheng,
Feng Yumei,
Earley Scott
Publication year - 2015
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.29.1_supplement.795.3
Subject(s) - medicine , stroke (engine) , endothelium , nitric oxide , endothelial stem cell , endothelial dysfunction , endocrinology , lesion , knockout mouse , cerebral circulation , pathology , chemistry , receptor , biochemistry , in vitro , mechanical engineering , engineering
The Ca 2+ ‐permeable transient receptor potential ankyrin 1 (TRPA1) channel is present in cerebral artery endothelial cells and mediates endothelium‐dependent dilation in response to oxidized lipid metabolites. Prior studies have shown that oxidative degradation of membrane lipids is increased in the vascular wall during hypertension. Therefore, we hypothesized that TRPA1 activity is enhanced in cerebral artery endothelial cells during hypertension and that augmented activity is protective against stroke. Hypertension was induced in control and endothelial cell specific TRPA1 knockout mice (eTRPA1 ‐/‐ ) by infusion of angiotensin II (1200 ng/kg/min, s.c.) and high salt (8%) diet. After two weeks of this treatment, the nitric oxide synthase inhibitor L‐NAME (120 mg/kg/day) was added to the drinking water to further increase mean arterial pressure (MAP). MAP was monitored by radiotelemetery and did not differ between groups under any conditions. All mice suffered fatal stroke. The survival time of eTRPA1 ‐/‐ mice (6‐22 days) was significantly less than that of control (3‐52 days) littermates (n = 19‐23). Histopathology revealed that eTRPA1 ‐/‐ mice developed more intracerebral hemorrhage (ICH) lesions than control mice (75 ± 1 total lesions per eTRPA1 ‐/‐ mouse vs. 50 ± 9 lesions per control mouse, n = 3‐4 per group). However, the volume of each lesion was smaller in eTRPA1 ‐/‐ mice (0.03 ± 0.01 mm 3 for eTRPA1 ‐/‐ vs. 0.12 ± 0.04 mm 3 for control, n = 3‐4). Together these data provide evidence that TRPA1 channels present in the cerebral endothelium are protective against hemorrhagic stroke associated with hypertension. Supported by HL091905 and 11SDG7360050.