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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/L130    most recent 90436.2008v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morin, C. Articles by Rousseau, E. Search for Related Content PubMed PubMed Citation Articles by Morin, C. Articles by Rousseau, E.

Relaxing effects of 17(18)-EpETE on arterial and airway smooth muscles in human lung

¹Le Bilarium, Department of Physiology and Biophysics, ²Service of Thoracic Surgery, and ³Department of Pathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada

Submitted 8 August 2008 ; accepted in final form 28 October 2008

Human cytochrome P-450 epoxygenase enzymes metabolize eicosapentaenoic acid (EPA), an -3-polyunsaturated fatty acid (PUFA), and leads to the production of 17(18)-epoxyeicosatetraenoic acid, or 17(18)-EpETE. The aim of the present study was to delineate the mode of action of 17(18)-EpETE on human pulmonary artery (HPA) and distal bronchi. Isometric tension measurements demonstrated that 17(18)-EpETE induced concentration-dependent relaxing effects in pulmonary artery and airway smooth muscles. Iberiotoxin (IbTx) and glyburide (Glyb), known BK_Ca and K_ATP channel inhibitors, respectively, reversed the relaxation induced by 17(18)-EpETE on both tissues types. Microelectrode measurements showed that exogenous addition of 17(18)-EpETE hyperpolarized the membrane potential of HPA and bronchial smooth muscle cells. These induced electrophysiological effects were reversed by the addition of 10 nM IbTx and 10 µM Glyb. Complementary experiments performed on human bronchi, using the planar lipid bilayer reconstitution technique, demonstrated that 17(18)-EpETE activated reconstituted BK_Ca channels at low free Ca²⁺ concentration. Moreover, in bronchi, the relaxing responses induced by 17(18)-EpETE were also related to reduced Ca²⁺ sensitivity of the myofilaments, since free Ca²⁺ concentration-response curves, performed on β-escin-permeabilized cultured explants, were shifted toward higher Ca²⁺. Together, these results provide new insight into the mode of action of 17(18)-EpETE in lung tissues and highlight this eicosanoid as a potent modulator of tone on both HPA and distal bronchi in vitro, which may be of clinical relevance in the pathophysiology of pulmonary hypertension and airway diseases.

17(18)-eicosatetraenoic acid; membrane potential; potassium channels; isometric tension; relaxation