title: Prostaglandin E₂ induced contraction of human intercostal arteries is mediated by the EP₃ receptor.
abstract: Arterial vascularization of the spinal cord may be mechanically or functionally altered during thoraco-abdominal surgery/intravascular procedures. Increased arterial pressure has been shown to restore spinal perfusion and function probably by increasing the blood flow through the intercostal arteries. The regulation of human intercostal artery (HICA) vascular tone is not well documented. Prostaglandin (PG)E(2) concentration is increased during inflammatory conditions and has been shown to regulate vascular tone in many preparations. In this context, the pharmacological response of HICA to PGE(2) and the characterization of the PGE(2) receptor subtypes (EP(1), EP(2), EP(3) or EP(4)) involved are of importance and that is the aim of this study. Rings of HICA were prepared from 29 patients and suspended in organ baths for isometric recording of tension. Cumulative concentration-response curves were performed in these preparations with various EP receptor agonists in the absence or presence of different receptor antagonists or inhibitors. PGE(2) induced the contraction of HICA (E(max)=7.28 ± 0.16 g; pEC(50) value=0.79 ± 0.18; n=17); contractions were also observed with the EP(3) receptor agonists, sulprostone, 17-phenyl-PGE(2), misoprostol or ONO-AE-248. In conclusion, PGE(2) induced vasoconstriction of HICA via EP(3) receptor subtypes and this result was confirmed by the use of selective EP receptor antagonists (L-826266, ONO-8713, SC-51322) and by a strong detection of EP(3) mRNA. These observations suggest that in the context of perioperative inflammation, increased PGE(2) concentrations could trigger vasoconstriction of HICA and possibly alter spinal vascularization.
authors.affiliation: INSERM, U698, Paris, F-75018, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gomez
authors.forename: Nabil
authors.initials: N
authors.lastname: Foudi
authors.forename: Gokce
authors.initials: G
authors.lastname: Topal
authors.forename: Malek
authors.initials: M
authors.lastname: Dhaouadi
authors.forename: Larissa
authors.initials: L
authors.lastname: Kotelevets
authors.forename: Eric
authors.initials: E
authors.lastname: Chastre
authors.forename: Xavier
authors.initials: X
authors.lastname: Norel
mesh_terms: D001158:Arteries; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D014662:Vasoconstrictor Agents; D015232:Dinoprostone