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http://purl.uniprot.org/citations/18952718http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18952718http://www.w3.org/2000/01/rdf-schema#comment"Hypertension is a major risk factor for stroke, but the factors that contribute to the increased incidence and severity of ischemic stroke in hypertension remain to be determined. 20-hydroxyeicosatetraenoic acid (20-HETE) has been reported to be a potent constrictor of cerebral arteries, and inhibitors of 20-HETE formation reduce infarct size following cerebral ischemia. The present study examined whether elevated production of 20-HETE in the cerebral vasculature could contribute to the larger infarct size previously reported after transient middle cerebral artery occlusion (MCAO) in hypertensive strains of rat [spontaneously hypertensive rat (SHR) and spontaneously hypertensive stroke-prone rat (SHRSP)]. The synthesis of 20-HETE in the cerebral vasculature of SHRSP measured by liquid chromatography-tandem mass spectrometry was about twice that seen in Wistar-Kyoto (WKY) rats. This was associated with the elevated expression of cytochrome P-450 (CYP)4A protein and CYP4A1 and CYP4A8 mRNA. Infarct volume after transient MCAO was greater in SHRSP (36+/-4% of hemisphere volume) than in SHR (19+/-5%) or WKY rats (5+/-2%). This was associated with a significantly greater reduction in regional cerebral blood flow (rCBF) in SHR and SHRSP than in WKY rats during the ischemic period (78% vs. 62%). In WKY rats, rCBF returned to 75% of control following reperfusion. In contrast, SHR and SHRSP exhibited a large (166+/-18% of baseline) and sustained (1 h) postischemic hyperperfusion. Acute blockade of the synthesis of 20-HETE with N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016; 1 mg/kg) reduced infarct size by 59% in SHR and 87% in SHRSP. HET0016 had no effect on the fall in rCBF during MCAO but eliminated the hyperemic response. HET0016 also attenuated vascular O2*-formation and restored endothelium-dependent dilation in cerebral arteries of SHRSP. These results indicate the production of 20-HETE is elevated in the cerebral vasculature of SHRSP and contributes to oxidative stress, endothelial dysfunction, and the enhanced sensitivity to ischemic stroke in this hypertensive model."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.org/dc/terms/identifier"doi:10.1152/ajpheart.00512.2008"xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Roman R.J."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Falck J."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Harder D.R."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Flasch A.K."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Dunn K.M."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/author"Renic M."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/name"Am J Physiol Heart Circ Physiol"xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/pages"H2455-65"xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/title"Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats."xsd:string
http://purl.uniprot.org/citations/18952718http://purl.uniprot.org/core/volume"295"xsd:string
http://purl.uniprot.org/citations/18952718http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18952718
http://purl.uniprot.org/citations/18952718http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18952718
http://purl.uniprot.org/uniprot/#_P08516-mappedCitation-18952718http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18952718
http://purl.uniprot.org/uniprot/#_P24464-mappedCitation-18952718http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18952718
http://purl.uniprot.org/uniprot/P08516http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18952718
http://purl.uniprot.org/uniprot/P24464http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18952718