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In hypertension CYP450A metabolite 20‐HETE exacerbates flow‐induced arteriolar constriction and promotes cerebrovascular inflammation
Author(s) -
Toth Peter,
Csiszar Anna,
Sosnowska Danuta,
Sonntag William E.,
Ungvari Zoltan,
Koller Akos
Publication year - 2012
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.26.1_supplement.853.24
Subject(s) - medicine , pathogenesis , inflammation , cerebral blood flow , constriction , blood pressure , endothelial dysfunction , cardiology , stroke (engine) , endocrinology , mechanical engineering , engineering
Hypertension impairs local regulation of cerebral blood flow by increasing vascular tone and inducing cerebrovascular inflammation thereby contributing to the pathogenesis of ischemic cerebrovascular diseases (i.e. stroke, vascular cognitive impairment). To test the hypothesis that 20‐hydroxyeicosatetraenic acid (20‐HETE) contributes to hypertension‐induced cerebrovascular alterations, we treated spontaneously hypertensive rats (SHR) with HET0016, an inhibitor of 20‐HETE synthesis. Although HET0016 decreased systolic blood pressure, the treated animals remained hypertensive. In cerebral arteries isolated from HET0016‐treated SHRs flow‐induced constriction was attenuated and endothelial dilation to acetylcholine was improved. HET0016 treatment inhibited cerebrovascular inflammation in SHRs as shown by the reduced expression of pro‐inflammatory cytokines TNF, IL‐1 and IL‐6. Taken together, in hypertension increased production of 20‐HETE contributes to cerebromicrovascular inflammation and dysfunction, which likely promote the pathogenesis of ischemic cerebrovascular diseases. Supported: AHA, Founders Aff., 0855910D, NIH PO‐1 HL‐43023, Hungarian Natl. Sci. Res. Fund (OTKA‐K71591, K67984 ), MHT 2011.