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

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 Fzo_2α 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 F_2α raCeptors on vascular smooth muscle.

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

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