Journal article
Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K+channels
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.281(1), pp.R246-R253
07/01/2001
DOI: 10.1152/ajpregu.2001.281.1.R246
PMID: 11404300
Abstract
Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 ± 7 μm) (means ± SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 μM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N G-nitro-l-arginine (100 μM) but was inhibited markedly by baicalein (10 μM) or nordihydroguaiaretic acid (NDGA; 10 μM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 μM arachidonate dilated the basilar artery by 19 ± 7 and 1 ± 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [3H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.
Details
- Title: Subtitle
- Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K+channels
- Creators
- Frank M Faraci - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242; andChristopher G Sobey - Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, AustraliaSophocles Chrissobolis - Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, AustraliaDonald D Lund - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242; andDonald D Heistad - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242; andNeal L Weintraub - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242; and
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.281(1), pp.R246-R253
- DOI
- 10.1152/ajpregu.2001.281.1.R246
- PMID
- 11404300
- NLM abbreviation
- Am J Physiol Regul Integr Comp Physiol
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Language
- English
- Date published
- 07/01/2001
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040370902771
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