Synergistic inhibitory effects of adrenoceptor antagonists and prostacyclin, and umbilical artery-derived prostacyclin-like activity on platelet aggregation.
Adrenoceptor antagonists are being used increasingly for the treatment of pregnancy-induced hypertension (PIH). Previous studies have shown that these drugs can inhibit platelet aggregation and thromboxane production. The aims of this study were to determine (i) whether adrenoceptor antagonists had any effect on vascular prostacyclin (PGI2) production and (ii) whether these drugs acted synergistically with PGI2 and the PGI2-like activity derived from umbilical artery to inhibit platelet aggregation in vitro. The adrenoceptor antagonists labetalol, pindolol and propranolol were found to have no effect on PGI2 production from the umbilical artery at low drug concentrations. These agents were also found to act synergistically with both pure PGI2 and PGI2-like activity derived from umbilical artery to inhibit platelet aggregation. This synergistic effect may be beneficial in the treatment of disorders which are associated with reduced PGI2 production, such as PIH where such synergy may help compensate for PGI2 deficiency.
Greer
I A
IA
Department of Obstetrics, Centre for Reproductive Biology, Endingburgh, Scotland, U.K.
McLaren
M
M
Forbes
C D
CD
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000096:biosynthesis; D000322:Adrenergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D011464:Epoprostenol / Q000502:physiology*; D005312:Fetal Blood / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D010974:Platelet Aggregation / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology
D000322:Adrenergic Agonists; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011433:Propranolol; D010869:Pindolol; D011464:Epoprostenol; D007741:Labetalol