Effect of beraprost sodium, a stable prostacyclin analogue, on pulmonary thromboembolism in mice

Abstract

Prostacyclin is the major metabolite generated during arachidonic acid infusion in the dog lung (1). Gryglewski et al. (2) demonstrated that prostacyclin is continuously generated and released from the cat lung in vivo. Thus it is considered that prostacyclin plays a key role in the modulation of vasomotor tone in lung (3), and may protect the pulmonary circulation against excessive vasoconstriction (4). Prostacyclin is less inactivated than prostaglandin E 1 (PGE 1 ) as it passes through pulmonary circulation (5). However, from a practical standpoint, its liability to metabolic degradation in vivo has limited its therapeutic application. Beraprost (sodium ((±)-1R * ,2R * ,3aS * ,8bS * )-2,3, 3a,8b-tetrahydro-2-hydroxyl-1-[(E)-(3S')-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta [b] benzofuran-5-butyrate) is a chemically stable prostacyclin analogue which can be administered orally and has been demonstrated to possess a similar pharmacological profile to prostacyclin, i.e., potent platelet aggregation inhibitory effect in vitro and ex vivo in various animal species (6,7), antithrombotic effect in the hamster cheek pouch (8) and vasodilating effects in the dog (9). In the present study, we have compared the effect of beraprost with some other antithrombotic agents and vasodilators on pulmonary thromboembolism in mice