Effects of U-46619 on pulmonary hemodynamics before and after administration of BM-573, a novel thromboxane A2 inhibitor

B Lambermont, P Kolh, J-M Dogné, A Ghuysen, V Tchana-Sato, P Morimont, P Benoit, P Gérard, B Masereel, R Limet, V D'Orio

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We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock.
Original languageEnglish
Pages (from-to)217-23
Number of pages7
JournalArchives of Physiology and Biochemistry
Issue number3
Publication statusPublished - Jul 2003


  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Animals
  • Blood Pressure
  • Drug Interactions
  • Female
  • Heart Rate
  • Male
  • Models, Cardiovascular
  • Pulmonary Artery
  • Pulmonary Circulation
  • Receptors, Thromboxane
  • Sulfonylurea Compounds
  • Swine
  • Thromboxane A2
  • Vasoconstrictor Agents


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