y-20811 and vapiprost

Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2 synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB. Both vapiprost and Y-20811 significantly prolonged the time required to complete suppression of the CAP as compared with saline as control. These findings indicate that TXA2 may play an important role in microcirculation disorders in the rat inner ear.

Topics: Action Potentials; Animals; Audiometry, Evoked Response; Biphenyl Compounds; Cochlea; Ear, Inner; Epoprostenol; Hearing Disorders; Heptanoic Acids; Imidazoles; Microcirculation; Platelet Aggregation; Rats; Rats, Wistar; Receptors, Thromboxane; Thromboxane A2; Thromboxane-A Synthase; Vasoconstriction

We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade.

Topics: Animals; Aspirin; Biphenyl Compounds; Disease Models, Animal; Femoral Artery; Fibrinolytic Agents; Guinea Pigs; Heptanoic Acids; Imidazoles; Light; Male; Microscopy, Electron, Scanning; Photochemistry; Platelet Aggregation; Prostaglandins; Rats; Rats, Wistar; Rose Bengal; Thrombosis