Antagonism of PGD 2 vasodepressor responses in the rat in vivo by the novel, selective antagonist, BW A868C

1 Bolus intravenous injection of prostaglandin D 2 (PGD 2 , 1–160μg kg −1 ), the hydantoin prostanoid BW245C (0.25–160 μg kg −1 ) or prostacyclin (PGI 2 , 0.05–0.5 μg kg −1 ) caused a dose‐dependent fall in systemic arterial blood pressure (BP) in the anaesthetized rat, lasting 2–4 min. 2 Intravenous infusion of the novel 3‐benzyl substituted hydantoin, BW A868C (1–10 μg kg −1 min −1 ), in doses that had no direct effect on BP, dose‐dependently reduced the vasodepressor action of PGD 2 . 3 Bolus injection of BW A868C (30 and 100 μg kg −1 , i.v.) likewise dose‐dependently antagonized the vasodepressor responses to PGD 2 , causing a 3.4 and 13.2 fold rightward shift of the dose‐response curve. 4 The thromboxane‐receptor antagonist, BM 13.177 (2.5 mg kg −1 i.v.) had little effect on the PGD 2 vasodepressor responses, suggesting minimal contribution of a PGD 2 interaction at thromboxane receptor‐sites in the systemic vasculature of this species. 5 BW A868C (10 μg kg −1 min −1 i.v.) caused a rightward shift (59 fold) of the dose‐response relationship for BW245C, the putative PGD 2 ‐receptor agonist. This antagonism lasted for at least 1h after termination of the BW A868C infusion. Higher doses of BW A868C (20–100 μg kg −1 min −1 ) caused no further antagonism of the vasodepressor responses to BW245C, suggesting that this prostanoid also acts at vascular receptors other than of the DP‐type. 6 BW A868C (10 μg kg −1 min −1 , i.v.) failed to alter the vasodepressor actions of prostacyclin. 7 These findings in the rat in vivo support the characterization of BW A868C as a potent and selective antagonist of the cardiovascular actions of PGD 2 at the DP‐receptor.