| pubmed-article:18952718 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0034705 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0005839 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0228174 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0242606 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0948008 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0439793 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0033268 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0205250 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C1880177 | lld:lifeskim |
| pubmed-article:18952718 | lifeskim:mentions | umls-concept:C0046616 | lld:lifeskim |
| pubmed-article:18952718 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:18952718 | pubmed:dateCreated | 2008-12-5 | lld:pubmed |
| pubmed-article:18952718 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:18952718 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18952718 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18952718 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18952718 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18952718 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18952718 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:18952718 | pubmed:issn | 0363-6135 | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:RomanRichard... | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:HarderDavid... | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:FlaschAveria... | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:FalckJohnJ | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:RenicMarijaM | lld:pubmed |
| pubmed-article:18952718 | pubmed:author | pubmed-author:DunnKathryn... | lld:pubmed |
| pubmed-article:18952718 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18952718 | pubmed:volume | 295 | lld:pubmed |
