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

Abstract

1Platelet-rich plasma (PRP) from humans, cats, dogs (after addition of 10 IM adrenaline), 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. 2 The stable thromboxane (Tx) analogues, 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 analogue. 3 CTA2 and the endoperoxide analogue 9,11-methanoepoxy PGH2 (U-46619) constricted coronary arteries from cats, dogs, rabbits and guinea-pigs, while sheep vessels were unresponsive to either analogue. 4 Vasoconstrictor responses to U-46619 were significantly attenuated by PTA2 in vessels from all species. However, constriction produced by CTA2 was blocked significantly only in vessels from cats, dogs and guinea-pigs. 5 These results demonstrate the species differences which exist in the responsiveness of platelets and coronary arteries to thromboxane and endoperoxide analogues. Furthermore, the results illustrate the importance of species selection in the study of thromboxane antagonists for potential therapeutic use.

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

“…We investigated any such correlation using platelets of different species; differences in the responsiveness of platelets to TXA2 analogues between species, especially rabbit platelets, has already been observed by several groups (Anderson & MacIntyre, 1982;Burke et al, 1983). In the present study we examined the sensitivity of human, dog and rabbit platelets to inhibition by ONO-11120 of arachidonic acid-induced aggregation.…”

“…Using these compounds, several groups have analysed the actions ofTXA2 on platelets and vascular as well as tracheal smooth muscles. These studies have suggested that TXA2 acts on a putative membrane receptor(s) to elicit its action, and based on different responsiveness of various systems to these compounds, multiplicity and differences in TXA2 receptors in various tissues and between species have been discussed (Lefer et al, 1980;Jones et al, 1982;Burke et al, 1983;Parise et al, 1984;Armstrong et al, 1985;Mais et al, 1985a).…”

Inhibitory Effect of KW-3635, a New Thromboxane A2-Receptor Antagonist, on Arterial Thrombosis in Guinea Pigs

“…The platelets from guinea pigs are quite similar to those from humans with regard to their response to agonists and antagonists of the prostaglandins (3). Therefore, there is fairly general agreement that the guinea pig is a suitable species for evaluating the antithrombotic effect of an agent.…”

Regional Vascular Responses to Thromboxane A2 Analogue and Their Blockade with Vapiprost, a Selective Thromboxane Receptor Blocking Drug, in Anesthetized Dogs

“…Results that vapiprost even at the highest dose employed in this study virtual ly had no effect on the baseline hemodynamics are also consistent with the previous data that this drug has no partial agonist activity (2,8), and suggest that the hemodynamic influence of tonic formation and release of TXA2, if any, is presumably negligible in the anes thetized open-chest dog, in contrast to the case of cyclo oxygenase inhibitors such as indomethacin, which has been found to cause an increase in vascular resistance (26,27). Therefore, these characteristics of vapiprost indicate that this drug is not only a pharmacological tool as a TP-receptor blocking agent but also may be useful in the treatment of patients with various car diovascular diseases such as transient ischemic attacks, unstable angina and Raynaud's disease that are consi dered to involve TXA2-induced vasoconstriction (1, 2), although it should be noted that species differences may exist in the responsiveness of platelets and vessels to TXA2 and endoperoxide analogues (28).…”