thromboxane-a2 and nizofenone

The effect of ozagrel, a selective thromboxane A(2) (TXA(2)) synthetase inhibitor, on the obstruction after cerebral ischemia-reperfusion was studied in experimental animal models. The reduced spontaneously locomotor activity and the obstruction of motor coordination were improved by the administration of ozagrel in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel suppressed the decrease in specific gravity of the brain tissue induced by the occlusion-reperfusion in the conscious cerebral ischemia-reperfusion SHR model, and recovered the postischemic decrease in cortical PO(2) after middle cerebral artery occlusion-reperfusion in cats. The level of TXB(2), a metabolite of TXA(2), in the brain increased after the cerebral ischemia-reperfusion, and ozagrel prevented this increase. Additionally, ozagrel also increased the level of 6-keto-PGF(1alpha), a metabolite of prostaglandin I(2) (PGI(2)), in the brain tissue after cerebral ischemia-reperfusion, and the administration of PGI(2) improved the reduced spontaneous locomotor activity in the conscious cerebral ischemia-reperfusion mouse model. Our data suggest that ozagrel suppressed the obstruction following cerebral ischemia-reperfusion by preserving the cerebral blood flow via preventing the increase in TXA(2) and causing an increase in the PGI(2) level.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Chemistry; Cerebral Cortex; Enzyme Inhibitors; Epoprostenol; Imidazoles; Ischemic Attack, Transient; Male; Methacrylates; Mice; Motor Activity; Neuroprotective Agents; Oxygen Consumption; Psychomotor Performance; Rats; Rats, Inbred SHR; Reperfusion Injury; Specific Gravity; Thromboxane A2; Thromboxane-A Synthase

The effect of nizofenone on prostacyclin synthesis was investigated using rat arterial walls. Incubation of arterial walls with [14C] arachidonic acid resulted in a time-dependent formation of prostacyclin, which was radiochromatographically detected as the stable breakdown product, 6-keto prostaglandin F1 alpha. The addition of nizofenone dose-dependently stimulated the prostacyclin formation, and significant increases of 47 and 106% were observed at 0.1 and 0.3 mM, respectively. No stimulation of prostaglandin E2 and thromboxane A2 synthesis was observed in the experiments with ram seminal vesicle microsomes and human platelet microsomes. These findings suggest that nizofenone has a selective stimulatory action on prostacyclin synthesis.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Arteries; Blood Platelets; Epoprostenol; Humans; Imidazoles; In Vitro Techniques; Ischemic Attack, Transient; Male; Rats; Seminal Vesicles; Sheep; Thromboxane A2