Article date: February 1989
By: S. Hamid‐Bloomfield, B.J.R. Whittle in Volume 96, Issue 2, pages 307-312
Bolus intravenous injection of prostaglandin D2 (PGD2, 1–160μg kg−1), the hydantoin prostanoid BW245C (0.25–160 μg kg−1) or prostacyclin (PGI2, 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.
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 PGD2.
Bolus injection of BW A868C (30 and 100 μg kg−1, i.v.) likewise dose‐dependently antagonized the vasodepressor responses to PGD2, causing a 3.4 and 13.2 fold rightward shift of the dose‐response curve.
The thromboxane‐receptor antagonist, BM 13.177 (2.5 mg kg−1 i.v.) had little effect on the PGD2 vasodepressor responses, suggesting minimal contribution of a PGD2 interaction at thromboxane receptor‐sites in the systemic vasculature of this species.
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 PGD2‐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.
BW A868C (10 μg kg−1 min−1, i.v.) failed to alter the vasodepressor actions of prostacyclin.
These findings in the rat in vivo support the characterization of BW A868C as a potent and selective antagonist of the cardiovascular actions of PGD2 at the DP‐receptor.
Bolus intravenous injection of prostaglandin D2 (PGD2, 1–160μg kg−1), the hydantoin prostanoid BW245C (0.25–160 μg kg−1) or prostacyclin (PGI2, 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.
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 PGD2.
Bolus injection of BW A868C (30 and 100 μg kg−1, i.v.) likewise dose‐dependently antagonized the vasodepressor responses to PGD2, causing a 3.4 and 13.2 fold rightward shift of the dose‐response curve.
The thromboxane‐receptor antagonist, BM 13.177 (2.5 mg kg−1 i.v.) had little effect on the PGD2 vasodepressor responses, suggesting minimal contribution of a PGD2 interaction at thromboxane receptor‐sites in the systemic vasculature of this species.
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 PGD2‐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.
BW A868C (10 μg kg−1 min−1, i.v.) failed to alter the vasodepressor actions of prostacyclin.
These findings in the rat in vivo support the characterization of BW A868C as a potent and selective antagonist of the cardiovascular actions of PGD2 at the DP‐receptor.
DOI: 10.1111/j.1476-5381.1989.tb11818.x
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