Effect of ridogrel on vascular contractions caused by vasoactive substances released during platelet activation

Ridogrel (6.3 x 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 x 10(-6) M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within 20 min of incubation of the blood vessel with the compound and easily reversible. Ridogrel antagonised contractions of isolated rabbit femoral arteries caused by prostaglandin F2 alpha in the same concentration range. Ridogrel also inhibited contractions induced by aggregating rat platelets on isolated rat caudal arteries (in the presence of ketanserin 4 x 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 F2 alpha receptors on vascular smooth muscle.