ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 137 citations in OpenAlex.
- Sex-dependent role of 20-HETE synthesis in outcome from ischemic stroke in rats.Physiological reports · 2026Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries.Life (Basel, Switzerland) · 2025Article
- Blood pressure and the brain: the conundrum of hypertension and dementia.Cardiovascular research · 2025Review
- 20-Hydroxyeicosatetraenoic Acid Regulates the Src/EGFR/NF-κB Signaling Pathway Via GPR75 to Activate Microglia and Promote TBI in the Immature Brain.Neurochemical research · 2024Article
- Candidate neuroinflammatory markers of cerebral autoregulation dysfunction in human acute brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Effect of Chronically Suppressed Plasma Angiotensin II on Regulation of the CYP4A/20-HETE Pathway in the Dahl Salt-Sensitive Rat.Antioxidants (Basel, Switzerland) · 2023Article
- Genetic Variants ofPharmacogenomics and personalized medicine · 2023Article
- Neuroprotective effects of Korean White ginseng and Red ginseng in an ischemic stroke mouse model.Journal of ginseng research · 2022Article
- The adducin saga: pleiotropic genomic targets for precision medicine in human hypertension-vascular, renal, and cognitive diseases.Physiological genomics · 2022Review
- 20-hydroxyeiscosatetraenoic acid may be as a predictor of malignant middle cerebral artery infarction in patients with massive middle cerebral artery infarction.BMC neurology · 2021Observational
- Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE.Clinical science (London, England : 1979) · 2021Review
- 20-HETE-promoted cerebral blood flow autoregulation is associated with enhanced pericyte contractility.Prostaglandins & other lipid mediators · 2021Article
- CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity.International journal of molecular sciences · 2021Article
- Increased 20-HETE Signaling Suppresses Capillary Neurovascular Coupling After Ischemic Stroke in Regions Beyond the Infarct.Frontiers in cellular neuroscience · 2021Article
- Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke.International journal of molecular sciences · 2020Review
- Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- 20-HETE Enzymes and Receptors in the Neurovascular Unit: Implications in Cerebrovascular Disease.Frontiers in neurology · 2020Article
- Neuroprotective effect ofChinese medicine · 2020Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
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.
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