Abstract
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 language | English |
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Pages (from-to) | 217-23 |
Number of pages | 7 |
Journal | Archives of Physiology and Biochemistry |
Volume | 111 |
Issue number | 3 |
DOIs | |
Publication status | Published - Jul 2003 |
Keywords
- 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