[Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in guinea pig trachea and lung tissue strips].
Thromboxane A2 (TxA2) is a potent platelet aggregator and vascular or 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 or relaxing responses in guinea pig trachea and lung tissue strips induced by various vasoactive substances. Fourteen guinea pigs, weighing 300-350 g, were sacrificed. Trachea and lungs 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 relaxing responses in guinea pig trachea strips were attenuated significantly by the continuous infusion of DP-1904 in a dose-dependent fashion. Arachidonic acid-induced contractile responses in guinea pig lung strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Acetylcholine-, histamine- and prostaglandin F2 alpha-induced contractile responses in guinea pig lung and trachea 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 the treatment of chronic obstructive lung diseases.
Shimizu
K
K
Kobayashi
J
J
Iwanaga
T
T
Kuratomi
Y
Y
Kitamura
S
S
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D015237:Dinoprost / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D006633:Histamine Antagonists; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D006633:Histamine Antagonists; D007093:Imidazoles; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D014662:Vasoconstrictor Agents; C056295:nafagrel; D015237:Dinoprost; D013930:Thromboxane-A Synthase; D000109:Acetylcholine