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Thromb Haemost 1990; 64(01): 091-096
DOI: 10.1055/s-0038-1647259
Original Article
Schattauer GmbH Stuttgart

Effect of Ridogrel on Vascular Contractions Gaused by Vasoactive Substances Released during Platelet Activation[*]

W J Janssens
The Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium
,
F J S Cools
The Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium
,
L A M Hoskens
The Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium
,
J M Van Nueten
The Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium
› Author Affiliations
Further Information

Publication History

Received 31 October 1989

Accepted after revision 07 May 1990

Publication Date:
25 July 2018 (online)

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Summary

Ridogrel (6.3 × 10−6 to 10−4 M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 × 10−6 M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within}D min of incubation of the blood vessel with the compound and easily reversible. Ridogrel antagonised contractions of isolated rabbit femoral arteries caused by prostaglandin Fzo2α in the same concentration range. Ridogrel also inhibited contractions induced by aggregating rat platelets on isolated rat caudal arteries (itt the presence of ketanserin 4 × 10−7 M) and on isolated rabbit pulmonary and femoral arteries (in the absence of ketanserin). Ridogrel had no effect on Ca2+-induced contractions in depolarised isolated rabbit femoral arteries, and at 10−4 M antagonised serotonin-induced contractions in this blood vessel. Its effect on serotonin-induced contractions was statistically significant but very small on isolated rat caudal arteries. These observations indicate that ridogrel is an antagonist of prostaglandin endoperoxide/thromboxane A2 and prostaglandin F2α raCeptors on vascular smooth muscle.

Dedicated to Professor M. Verstraete on the occasion of his 65th birthday.


 

  • References

  • 1 De Clerck F, Beetens J, de Chaffoy de Courcelles D, Freyne E, Janssen PA J. R68070: Thromboxane A2 synthetase inhibition and thromboxane A2/prostaglandin endoperoxide receptor blockade combined in one molecule I. Biochemical profile in vitro. Thromb Haemostas 1989; 61: 35-42
    PubMedGoogle Scholar
  • 2 De Clerck F, Beetens J, Van de Water A, Vercammen E, Janssen PA J. R68070: Thromboxane A2 synthetase inhibition and thromboxane A2/prostaglandin endoperoxide receptor blockade combined in one molecule II. Pharmacological effects in vivo and ex vivo. Thromb Haemostas 1989; 61: 43-49
    PubMedGoogle Scholar
  • 3 Jaschonek K, Muller CP. Platelet and vessel associated prostacyclin and thromboxane A2/prostaglandin endoperoxide receptors. Eur J Clin Investigation 1988; 18: 1-8
    PubMedGoogle Scholar
  • 4 Hung SC, Ghali NI, Venton DL, Le Breton GC. Prostaglandin F12α antagonises thromboxane A2induced-induced human platelet aggregation. Prostaglandins 1982; 24: 195-206
    CrossrefPubMedGoogle Scholar
  • 5 De Clerck F, Van Nueten JM. Platelet-mediated vascular contractions: inhibition of the serotonergic component by ketanserin. Thromb Res 1982; 27: 713-727
    CrossrefPubMedGoogle Scholar
  • 6 Arunlakshana O, Schild HO. Some quantitative uses of drug antagonist. Br J Pharmacol 1959; 14: 48-58
    PubMedGoogle Scholar
  • 7 Mullane KM, Bradley G, Moncada S. The interactions of platelet-derived mediators on canine coronary arteries. Eur J Pharmacol 1982; 84: 115-118
    CrossrefPubMedGoogle Scholar
  • 8 Van Nueten JM, Janssens WJ, Vanhoutte PM. Serotonin and vascular reactivity. Pharmacol Res Commun 1985; 17: 585-608
    CrossrefPubMedGoogle Scholar
  • 90 Vanhoutte PM, Van Nueten JM, Janssens WJ. The role of the endothelium in the cardiovascular response to serotonin. Serotonin, from cell biology to pharmacology and therapeutics Kluwer Academic Publishers; 1990: 81-96
    Google Scholar
  • 10 Janssens WJ, Van Nueten JM. Amplifying effect of serotonin in the control of vascular tone. Serotonin, from cell biology to pharmacology and therapeutics Kluwer Academic Publishers; 1990: 69-76
    Google Scholar
  • 11 Janssens WJ, Van Nueten JM. Vasoconstrictor effects of aggregating platelets in rabbit pulmonary arteries with and without endothelium. Thromb Haemostas 1987; 58: 153 (Abstr).
    PubMedGoogle Scholar
  • 12 De Freyn G, Deckmyn H, Vermylen J. A thromboxane synthetase inhibitor reorients endoperoxide metabolism in whole blood towards prostacyclin and prostaglandin E2. Thromb Res 1982; 26: 389-400
    CrossrefPubMedGoogle Scholar
  • 13 Furchgott RF, Vanhoutte PM. Endothelium-derived relaxing and contracting factors. Faseb J 1989; 3: 2007-2018
    CrossrefPubMedGoogle Scholar
  • 14 Janssens WJ, Deckmyn H, Gresele P, Vermylen J. BM 13.177 Selectively inhibits endoperoxide analogue induced vascular contractions. Arch Int Pharmacodyn 1985; 276: 28-34
    PubMedGoogle Scholar
  • 15 Verheyen A, Lauwers F, Vlaminckx E, De Clerck F. Differential vasoreactivity to the thromboxane A2 mimic U46619 of collateral and normal peripheral blood vessel in in situ perfused rat hindquarters. Blood Vessels 1989; 26: 165-176
    PubMedGoogle Scholar