Sodium 5-(3′-pyridinylmethyl)benzofuran-2-carboxylate (U-63557A) potentiates protective effect of intravenous eicosapentaenoic acid on impaired CBF in ischemic gerbils

Abstract

✓ Eicosapentaenoic acid (EPA) has been reported to improve postischemic cerebral blood flow (CBF). The present study was designed to determine whether sodium 5-(3′-pyridinylmethyl)benzofuran-2-carboxylate (U-63557A), a selective thromboxane synthetase inhibitor, could potentiate the effects of EPA on CBF in ischemic gerbils. Ischemia was produced by bilateral carotid artery occlusion for 15 minutes followed by reperfusion for 2 hours. Immediately after ischemia, gerbils were given either an intravenous bolus of 0.167 mg of EPA followed by a continuous infusion of EPA at 1 mg/hr, or U-63557A (10 mg/kg intraperitoneally), or U-63557A and EPA, or a saline infusion. Regional CBF was measured by the hydrogen clearance method, and brain water by the specific gravity technique. Brain prostaglandins were measured by radioimmunoassay. Preischemic CBF's ranged from 27.4 to 29.5 ml/100 gm/min for the four animal groups. After ischemia and 2 hours of reperfusion, CBF in the saline-infused gerbils was significantly decreased to 19.2 ml/100 gm/min. Gerbils treated with either EPA or U-63557A alone had a CBF of 23.7 and 21.6 ml/100 gm/min, respectively. Postischemic CBF in animals treated with both U-63557A and EPA was 30.0 ml/100 gm/min, significantly higher than in saline-infused gerbils. Brain levels of 6-keto prostaglandin (PG)F1α (the metabolite of PGI2) were significantly higher in gerbils treated with U-63557A and EPA compared to gerbils given EPA alone. This study indicates that U-63557A potentiates the effects of EPA on postischemic CBF. This is probably due to the ability of U-63557A to increase prostacyclin formation in the vessel wall.