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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1435    most recent 01115.2007v1 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.

Effects of -hydroxylase product on distal human pulmonary arteries

¹Le Bilarium, Department of Physiology and Biophysics, ²Service of Thoracic Surgery, and ³Department of Pathology, Université de Sherbrooke, Sherbrooke, Quebéc, Canada; and ⁴Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et de la Recherche Médicale U885, Université Bordeaux 2, Bordeaux, France

Submitted 25 September 2007 ; accepted in final form 7 January 2008

The aim of the present study was to provide a mechanistic insight into how 20-hydroxyeicosatetraenoic acid (20-HETE) relaxes distal human pulmonary arteries (HPAs). This compound is produced by -hydroxylase from free arachidonic acid. Tension measurements, performed on either fresh or 1 day-cultured pulmonary arteries, revealed that the contractile responses to 1 µM 5-hydroxytryptamine were largely relaxed by 20-HETE in a concentration-dependent manner (0.01–10 µM). Iberiotoxin pretreatments (10 nM) partially decreased 20-HETE-induced relaxations. However, 10 µM indomethacin and 3 µM SC-560 pretreatments significantly reduced the relaxations to 20-HETE in these tissues. The relaxing responses induced by the eicosanoid were likely related to a reduced Ca²⁺ sensitivity of the myofilaments since free Ca²⁺ concentration ([Ca²⁺])-response curves performed on β-escin-permeabilized cultured explants were shifted toward higher [Ca²⁺]. 20-HETE also abolished the tonic responses induced by phorbol-ester-dibutyrate (a PKC-sensitizing agent). Western blot analyses, using two specific primary antibodies against the PKC-potentiated inhibitory protein CPI-17 and its PKC-dependent phosphorylated isoform pCPI-17, confirmed that 20-HETE interferes with this intracellular process. We also investigated the effect of 20-HETE on the activation of Rho-kinase pathway-induced Ca²⁺ sensitivity. The data demonstrated that 20-HETE decreased U-46619-induced Ca²⁺ sensitivity on arteries. Hence, this observation was correlated with an increased staining of p116^Rip, a RhoA-binding protein. Together, these results strongly suggest that the 20-hydroxyarachidonic acid derivative is a potent modulator of tone in HPAs in vitro.

20-hydroxyeicosatetraenoic acid; calcium sensitivity; tension measurement