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INCREASED PRODUCTION OF THE ARACHIDONIC ACID METABOLITE 20‐HETE CONTRIBUTES TO HYPERTENSION‐INDUCED CEREBROVASCULAR ALTERATIONS
Author(s) -
Toth Peter,
Csiszar Anna,
Sosnowska Danuta,
Tucsek Zsuzsanna,
Cseplo Peter,
Springo Zsolt,
Tarantini Stefano,
Sonntag William E,
Ungvari Zoltan,
Koller Akos
Publication year - 2013
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.27.1_supplement.700.9
Subject(s) - vasomotor , arachidonic acid , oxidative stress , endocrinology , medicine , metabolite , inflammation , reactive oxygen species , chemistry , blood pressure , pharmacology , biochemistry , enzyme
Hypertension increases oxidative stress and inflammation in cerebral arteries and impairs vasomotor function. We tested the hypothesis that increased production of the arachidonic acid metabolite 20‐hydroxy‐5,8,11,14‐eicosatetraenoic acid (20‐HETE) contributes to hypertension‐induced cerebrovascular alterations. Male spontaneously hypertensive rats (SHR) were treated with HET0016, an inhibitor of 20‐HETE synthesis. In middle cerebral arteries (MCAs) of SHRs vasomotor responses were obtained and cellular production of reactive oxygen species (ROS), inflammatory cytokine expression and NF‐κB activation were assessed. Treated SHRs remained hypertensive, although their blood pressure was decreased compared to control SHRs. In MCAs of SHRs flow‐induced constriction was augmented and acetylcholine‐and ATP‐induced dilations were impaired. These alterations were reversed by HET0016. In MCAs of SHRs HET0016 decreased ROS level and inhibited inflammation and NF‐κB activation. Also, 20‐HETE significantly increased vascular production of ROS and promoted NF‐κB activation in cultured cerebromicrovascular endothelial cells. Inhibition of 20‐HETE synthesis in hypertension elicits reduction in blood pressure, anti‐oxidative, anti‐inflammatory effects and improve vasomotor function of cerebral arteries potentiating cerebrovascular protection.