title: Endothelin-dependent vasoconstriction in human uterine artery: application to preeclampsia.
abstract: BACKGROUND
  Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries.
  
  
  RESULTS
  Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination.
  
  
  CONCLUSIONS
  Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion.
authors.affiliation: INSERM U637, Université Montpellier 1, Montpellier, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Dechanet
authors.forename: Aurélie
authors.initials: A
authors.lastname: Fort
authors.forename: Elisabet
authors.initials: E
authors.lastname: Barbero-Camps
authors.forename: Hervé
authors.initials: H
authors.lastname: Dechaud
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
authors.forename: Anne
authors.initials: A
authors.lastname: Virsolvy
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D055988:Uterine Artery / Q000187:drug effects* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D004095:Dihydropyridines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins