Relaxation of Subarachnoid Hemorrhage-Induced Spasm by Eicosapentanoic Acid

ABSTRACT

OBJECTIVE: There is increasing evidence that the omega-3 polyunsaturated fatty acid, eicosapentanoic acid(EPA), induces relaxation in vessels from various animal models as cardiovascular protective nutrients. In vivo study was undertaken to investigate the potential therapeutic application of EPA to resolve vasospasm. METHODS: The basilar artery was visualized using transclival exposure, and its diameter monitored using videomicroscopy. Rabbits were divided randomly into seven groups1) normal rabbits basilar artery treated with topical application of 100nM/L EPA only;2) normal rabbits basilar artery treated with 20nM/L phorbol dibutyrate(PDB), then 20 nM/L PDB+100nM/L EPA;3) normal rabbits basilar artery treated with 80mM/L KCL, then 80mM/L KCL+100nM/L EPA;4) normal rabbits basilar artery treated with 20nM/L endothelin 1(ET-1) only;5) normal rabbits basilar artery treated with 20nM/L ET-1, then 20nM/L ET-1+100nM/L EPA;6) subarachnoid hemorrhage(SAH) rabbits basilar artery treated with artificial CSF only;7) SAH rabbits basilar artery treated with 100nM/L EPA. RESULTS: In normal(non-SAH) rabbits, EPA1) had no effect on basal tone;2) did not reverse KCL or PDB-induced constriction;and 3) substantially reversed ET-1-induced constriction. The diameter of normal rabbit basilar artery was 779.1+/-17.9nm(mean+/-standard error). After SAH, the mean diameter was 521.0+/-32.5nm. The addition of EPA reversed this SAH-induced constriction to 80.4% of baseline diameter. CONCLUSION: These results suggest that EPA induces relaxation in cerebrovascular arteries constricted with ET-1, and that it prevents and partially reverses SAH-induced vasoconstriction.