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(Circulation Research. 2007;101:176.)
© 2007 American Heart Association, Inc.

Cellular Biology

Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel

Nicolas Blondeau^*, Olivier Pétrault^*, Stella Manta, Valérie Giordanengo, Pierre Gounon, Régis Bordet, Michel Lazdunski, Catherine Heurteaux

From the Institut de Pharmacologie Moléculaire et Cellulaire (N.B., O.P., S.M., V.G., M.L., C.H.), UMR6097, CNRS Université de Nice Sophia Antipolis, Institut Paul Hamel, Valbonne; Centre Commun de Microscopie Appliquée (P.G.), Université de Nice - Sophia Antipolis; Département de Pharmacologie Médicale (R.B.), EA 1046, Institut de Médecine Prédictive et de Recherche Thérapeutique (IMPRT), Faculté de Médecine de l’Université de Lille 2, Centre Hospitalier, Universitaire de Lille, Lille Cedex, France.

Correspondence to Catherine Heurteaux, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR 6097, Institut Paul Hamel, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France. E-mail heurteaux{at}ipmc.cnrs.fr

Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially -linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly -linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. -Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1^–/– mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as -linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.

Key Words: cerebral ischemia • -linolenic acid • CBF • vasodilatation • two pore-domains channel TREK-1

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