| Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels. | |
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MedLine Citation:
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PMID: 19304946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epoxyeicosatrienoic acids (EETs) are potent vasodilators produced from arachidonic acid by cytochrome P-450 (CYP) epoxygenases and metabolized to vicinal diols by soluble epoxide hydrolase (sEH). In the brain, EETs are produced by astrocytes and the vascular endothelium and are involved in the control of cerebral blood flow (CBF). Recent evidence, however, suggests that epoxygenases and sEH are present in perivascular vasodilator nerve fibers innervating the cerebral surface vasculature. In the present study, we tested the hypothesis that EETs are nerve-derived relaxing factors in the cerebral circulation. We first traced these fibers by retrograde labeling in the rat to trigeminal ganglia (TG) and sphenopalatine ganglia (SPG). We then examined the expression of CYP epoxygenases and sEH in these ganglia. RT-PCR and Western blot analysis identified CYP2J3 and CYP2J4 epoxygenase isoforms and sEH in both TG and SPG, and immunofluorescence double labeling identified CYP2J and sEH immunoreactivity in neuronal cell bodies of both ganglia. To evaluate the functional role of EETs in neurogenic vasodilation, we elicited cortical hyperemia by electrically stimulating efferent cerebral perivascular nerve fibers and by chemically stimulating oral trigeminal fibers with capsaicin. Cortical blood flow responses were monitored by laser-Doppler flowmetry. Local administration to the cortical surface of the putative EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (30 mumol/l) attenuated CBF responses to electrical and chemical stimulation. These results suggest that EETs are produced by perivascular nerves and play a role in neurogenic vasodilation of the cerebral vasculature. The findings have important implications to such clinical conditions as migraine, vasospasm after subarachnoid hemorrhage, and stroke. |
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Authors:
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Jeffrey J Iliff; Ruikang Wang; Darryl C Zeldin; Nabil J Alkayed |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2009-03-20 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 296 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-04 Completed Date: 2009-06-19 Revised Date: 2011-10-18 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1352-63 Citation Subset: IM |
Affiliation:
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Dept. of Anesthesiology and Peri-Operative Medicine, Oregon Health and Science Univ., 3181 SW Sam Jackson Pk. Rd., UHS-2, Portland, OR 97239-3098, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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8,11,14-Eicosatrienoic Acid
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analogs & derivatives,
pharmacology Animals Capsaicin / pharmacology Cerebral Cortex / blood supply* Cerebrovascular Circulation* / drug effects Cytochrome P-450 Enzyme System / metabolism Eicosanoids / metabolism* Electric Stimulation Epoxide Hydrolases / metabolism Hyperemia / metabolism, physiopathology Laser-Doppler Flowmetry Male Middle Cerebral Artery / drug effects, innervation*, ultrasonography Neurons / drug effects, enzymology, metabolism* Rats Rats, Wistar Trigeminal Ganglion / drug effects, enzymology, metabolism* Vasodilation* / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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1-R01-HL-093140-01/HL/NHLBI NIH HHS; F31 NS060498-01/NS/NINDS NIH HHS; F31 NS060498-02/NS/NINDS NIH HHS; F31-NS-060498/NS/NINDS NIH HHS; P01 NS049210-050001/NS/NINDS NIH HHS; P01-NS-049210/NS/NINDS NIH HHS; R01 HL093140-01/HL/NHLBI NIH HHS; R01 HL093140-05/HL/NHLBI NIH HHS; R01 NS044313-08/NS/NINDS NIH HHS; R01-NS-044313/NS/NINDS NIH HHS; Z01 ES025034-13/ES/NIEHS NIH HHS; Z01-ES-025034/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyp2j4 protein, rat; 0/Eicosanoids; 404-86-4/Capsaicin; 7324-41-6/8,11,14-Eicosatrienoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; 98893-66-4/14,15-episulfide eicosatrienoic acid; EC 1.14.14.1/Cyp2j3 protein, rat; EC 3.3.2.-/Epoxide Hydrolases |
| Comments/Corrections | |
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