This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heizer, M. L. Articles by Ellis, E. F. Search for Related Content PubMed PubMed Citation Articles by Heizer, M. L. Articles by Ellis, E. F.

Stroke, Vol 22, 1389-1393, Copyright © 1991 by American Heart Association

ARTICLES

14,15-Epoxyeicosatrienoic acid inhibits platelet aggregation in mouse cerebral arterioles

ML Heizer, JS McKinney and EF Ellis
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.

BACKGROUND AND PURPOSE: Epoxygenase metabolites of arachidonic acid are produced by several tissues and have been shown to inhibit in vitro platelet aggregation. The purpose of the present investigation was to determine whether 14,15- or 8,9-epoxyeicosatrienoic acid, epoxygenase derivatives of arachidonic acid, affect the speed of platelet aggregation in in vivo mouse cerebral arterioles. METHODS: We performed a craniectomy in 116 anesthetized male mice and observed the pial arterioles by microscopy. We induced in situ platelet aggregation using a mercury light and intravascularly injected fluorescein dye. RESULTS: Indomethacin (0.5 mg/kg i.p.), a known cyclooxygenase inhibitor, and 14,15-epoxyeicosatrienoic acid (0.3 mg/kg i.v.) increased the time necessary for the light plus dye to induce the first arterial platelet aggregate by 35% and 26%, respectively, whereas 8,9-epoxyeicosatrienoic acid (0.3 mg/kg i.v.) had no effect. Analysis of mouse serum by radioimmunoassay showed that the degree of inhibition of platelet aggregation by indomethacin and epoxyeicosatrienoic acids correlated with the degree of inhibition of thromboxane production. CONCLUSIONS: We conclude that 14,15-epoxyeicosatrienoic acid is a potent inhibitor of in vivo platelet aggregation but cannot conclusively confirm that its effect on aggregation occurs via its reduction of platelet thromboxane A2. Because epoxyeicosatrienoic acids are produced by several tissues, including brain and vascular tissue, they may be important in vivo modulators of platelet aggregation and hemostasis.

This article has been cited by other articles:

				M. J. Corenblum, V. E. Wise, K. Georgi, B. D. Hammock, P. A. Doris, and M. Fornage Altered Soluble Epoxide Hydrolase Gene Expression and Function and Vascular Disease Risk in the Stroke-Prone Spontaneously Hypertensive Rat Hypertension, February 1, 2008; 51(2): 567 - 573. [Abstract] [Full Text] [PDF]

				I. P. Koerner, R. Jacks, A. E. DeBarber, D. Koop, P. Mao, D. F. Grant, and N. J. Alkayed Polymorphisms in the Human Soluble Epoxide Hydrolase Gene EPHX2 Linked to Neuronal Survival after Ischemic Injury J. Neurosci., April 25, 2007; 27(17): 4642 - 4649. [Abstract] [Full Text] [PDF]

				A. Luria, S. M. Weldon, A. K. Kabcenell, R. H. Ingraham, D. Matera, H. Jiang, R. Gill, C. Morisseau, J. W. Newman, and B. D. Hammock Compensatory Mechanism for Homeostatic Blood Pressure Regulation in Ephx2 Gene-disrupted Mice J. Biol. Chem., February 2, 2007; 282(5): 2891 - 2898. [Abstract] [Full Text] [PDF]

				M. Fornage, C. R. Lee, P. A. Doris, M. S. Bray, G. Heiss, D. C. Zeldin, and E. Boerwinkle The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke Hum. Mol. Genet., October 1, 2005; 14(19): 2829 - 2837. [Abstract] [Full Text] [PDF]

				J. D. Imig Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases Am J Physiol Renal Physiol, September 1, 2005; 289(3): F496 - F503. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				M. Fornage, E. Boerwinkle, P. A. Doris, D. Jacobs, K. Liu, and N. D. Wong Polymorphism of the Soluble Epoxide Hydrolase Is Associated With Coronary Artery Calcification in African-American Subjects: The Coronary Artery Risk Development In Young Adults (CARDIA) Study Circulation, January 27, 2004; 109(3): 335 - 339. [Abstract] [Full Text] [PDF]

				N. J. Alkayed, T. Goyagi, H.-D. Joh, J. Klaus, D. R. Harder, R. J. Traystman, and P. D. Hurn Neuroprotection and P450 2C11 Upregulation After Experimental Transient Ischemic Attack Stroke, June 1, 2002; 33(6): 1677 - 1684. [Abstract] [Full Text] [PDF]

				R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]