Thromb Haemost 1992; 68(04): 460-463
DOI: 10.1055/s-0038-1646297
Original Article
Schattauer GmbH Stuttgart

Comparison of the Inhibitory Effects of the TXA2 Receptor Antagonist, Vapiprost, and Other Antiplatelet Drugs on Arterial Thrombosis in Rats: Possible Role of TXA2

Yoshiharu Takiguchi
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Kouichirou Wada
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Mitsuyoshi Nakashima
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
› Author Affiliations
Further Information

Publication History

Received 06 November 1991

Accepted after revision 04 May 1992

Publication Date:
04 July 2018 (online)

Summary

The antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited collagen-induced rat platelet aggregation in whole blood ex vivo, in a dose-dependent manner. The potency ranking of antithrombotic effect was vapiprost > ketanserin (serotonin 5-HT2 receptor antagonist) >> ticlopidine (inhibitor of ADP-induced platelet aggregation) = dipyridamole (adenosine uptake inhibitor) >aspirin (cyclooxygenase inhibitor). On the other hand, the ranking of antiplatelet effect was ticlopidine ≥vapiprost ≥aspirin. Ketanserin and dipyridamole were ineffective. Relative to their antiplatelet effect, vapiprost and ketanserin had powerful antithrombotic effects. It is possible that the potent antithrombotic effects of vapiprost and ketanserin in vivo reflect the ability of these drugs to inhibit mediator-induced vascular contractions in addition to platelet aggregation. The results of the present study also suggest that TXA2 may play an important role in thrombogenesis in rats.

 
  • REFERENCES

  • 1 Furchgott RF. Role of endothelium in responses of vascular smooth muscle. Circ Res 1983; 53: 557-573
  • 2 De Clerck F, Van Nueten JM. Platelet-mediated vascular contractions: inhibition of the serotonergic component by ketanserin. Thromb Res 1982; 27: 713-727
  • 3 Van Nueten JM, Janssens WJ, Vanhoutte PM. Serotonin and vascular reactivity. Pharmacol Res Commun 1985; 17: 585-608
  • 4 Janssens WJ, Cools FJS, Hoskens LAM, Van Nueten JM. Effect of ridogrel on vascular contractions caused by vasoactive substances released during platelet activation. Thromb Haemostas 1990; 64: 91-96
  • 5 Lumley P, White BP, Humphrey PPA. GR32191, a highly potent and specific thromboxane A2 receptor blocking drug on platelets and vascular and airways smooth muscle in vitro. Br J Pharmacol. 1989; 97: 783-794
  • 6 Matsuno H, Uematsu T, Nagashima S, Nakashima M. Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J Pharmacol Methods 1991; 25: 303-318
  • 7 Challcn A, Branch WJ, Cummings JH. Quantitation of platelet mass during aggregation in the electronic (Wellcome) whole blood aggregometer. J Pharmacol Methods 1982; 8: 115-122
  • 8 Mallarkey G, Smith GM. A comparative study of the involvement of the prostaglandin H2/thromboxane A2 pathway in intravascular platelet aggregation in guinea-pigs and rats. Br J Pharmacol. 1985; 84: 425-430
  • 9 Emms H, Lewis GP. The roles of prostaglandin endoperoxide, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation in man and rat. Br J Pharmacol. 1986; 87: 109-115
  • 10 Panak E, Maffrand JP, Picard-Fraire C, Vallee E, Blanchard J, Roncucci R. Ticlopidine: a promise for the prevention and treatment of thrombosis and its complications. Haemostasis 1983; 13, suppl 1: 01-54
  • 11 Smith GM. Involvement of 5-hydroxytryptamine in platelet aggregation in vivo in rats and guinea-pigs. Thromb Haemostas 1989; 61: 463-467
  • 12 Buczko W, Gambino MC, De Gaetano G. Prolongation of rat tail bleeding time by ketanserin: mechanisms of action. Eur J Pharmacol 1984; 103: 261-268
  • 13 Maffrand JP, Bernat A, Delebassee D, Defreyn G, Cazenave JP, Gordon JL. ADP plays a key role in thrombogenesis in rats. Thromb Haemostas 1988; 59: 225-230
  • 14 Massad L, Plotkine M, Capdeville C, Boulu RG. Electrically induced arterial thrombosis model in the conscious rat. Thromb Res 1987; 48: 01-10
  • 15 Kelton JG, Hirsch J, Donati MB, De Buchanan MR. Thrombogenic effect of high-dose aspirin in rabbits. J Clin Invest 1978; 62: 892-895
  • 16 Wu KK, Chen YC, Fordman E, Ts’ao CH, Rayudu G, Matayoshi D. Differential effects of two doses of aspirin on platelet vessel wall interaction in vivo. J Clin Invest 1981; 68: 382-387
  • 17 Didisheim P. Inhibition by dipyridamole of arterial thrombosis in rats. Thromb Diathes Haemorrh 1968; 20: 256-266