Responsiveness of platelets and coronary arteries from different species to synthetic thromboxane and prostaglandin endoperoxide analogues

Abstract

Platelet-rich plasma (PRP) from humans, cats, dogs (after addition of 10 .mu.M adrenaline [epinephrine]), rabbits and guinea pigs aggregated in response to sodium arachidonate or 9,11-azo-prostaglandin H2, while PRP obtained from sheep was unresponsive to either agent. The stable thromboxane (Tx) analogs, carbocyclic TxA2 (CTA2) and pinane TxA2 (PTA2) significantly inhibited these aggregatory responses in platelets from humans, dogs and guinea pigs, while PTA2 but not CTA2 produced significant inhibition in cat platelets. The aggregatory response of PRP from rabbits was not significantly blocked by either analog. CTA2 and the endoperoxide analog 9,11-methanoepoxy PGH2 (U-46619) constricted coronary arteries from cats, dogs, rabbits and guinea pigs, while sheep vessels were unresponsive to either analog. Vasoconstrictor responses to U-46619 were significantly attenuated by PTA2 in vessels from all species. Constriction produced by CTA2 was blocked significantly only in vessels from cats, dogs and guinea pigs. These results demonstrate the species differences which exist in the responsiveness of platelets and coronary arteries to thromboxane and endoperoxide analogs. The results illustrate the importance of species selection in the study of thromboxane antagonists for potential therapeutic use.