Endothelial cell TRPA1 activity exacerbates cerebral hemorrhage during severe hypertension

• DOI: 10.3389/fmolb.2023.1129435
• Publication Date: 2023-01-30T05:45:26Z
• Authors: Michelle N. Sullivan; Pratish Thakore; Vivek Krishnan; Sushma Alphonsa; Wencheng Li; Yumei Feng Earley; Scott Earley
• Keywords: Electrical impedance myography; Cerebral circulation

Introduction: Hypoxia-induced dilation of cerebral arteries orchestrated by Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) cation channels on endothelial cells is neuroprotective during ischemic stroke, but it unknown if the channel has a similar impact hemorrhagic stroke. TRPA1 are endogenously activated lipid peroxide metabolites generated reactive oxygen species (ROS). Uncontrolled hypertension, primary risk factor for development associated with increased ROS production and oxidative stress. Therefore, we hypothesized that activity Methods: Severe, chronic hypertension was induced in control (Trpa1fl/fl) cell-specific knockout (Trpa1-ecKO) mice using combination angiotensin II administration, high-salt diet, addition nitric oxide synthase inhibitor to drinking water. Blood pressure measured awake, freely-moving surgically placed radiotelemetry transmitters. TRPA1-dependent artery evaluated myography, expression NADPH oxidase (NOX) isoforms from both groups determined PCR Western blotting techniques. In addition, generation capacity lucigenin assay. Histology performed examine intracerebral hemorrhage lesion size location. Results: All animals became hypertensive, majority developed hemorrhages or died causes. Baseline blood responses hypertensive stimulus did not differ between groups. Expression altered after 28 days treatment, three NOX animals. NOX-dependent activation dilated greater extent compared controls. The number lesions Trpa1-ecKO were significantly smaller mice. Morbidity mortality Discussion: We conclude cell increases flow resulting extravasation events; however, this effect does overall survival. Our data suggest blocking may be helpful treating hypertension-associated stroke clinical setting.