[Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in rabbit blood vessel smooth muscle preparations].
Thromboxane A2 (TxA2) is a potent platelet aggregator as well as a vascular and bronchial constrictor. DP-1904, a newly synthesized imidazol TxA2 synthetase inhibitor, is a potent and long-acting agent. The present investigation was conducted to explore the effect of DP-1904 on the contractile responses in rabbit pulmonary artery and descending aorta strips induced by various vasoactive substances. Fourteen Japanese albino rabbits, weighing about 3 kg, were sacrificed. Rabbit pulmonary artery and descending aorta were removed, cut spirally, set up in bioassay glass jackets and superfused with Krebs-Henseleit solution at 37 degrees C, saturated with oxygen and carbon dioxide. Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder. Arachidonic acid-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904 in a dose-dependent fashion. Prostaglandin F2 alpha-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Angiotensin II-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Norepinephrine-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. The above results suggest that DP-1904 might be a useful therapeutic agent for treatment of pulmonary hypertension in patients with chronic obstructive lung diseases.
Shimizu
K
K
Kobayashi
J
J
Iwanaga
T
T
Kuratomi
Y
Y
Kitamura
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C056295:nafagrel; D013930:Thromboxane-A Synthase