Effect of YM-254890, a specific Gαq/11 inhibitor, on experimental peripheral arterial disease in rats

Abstract The protective effect of YM-254890, a specific Gα q/11 inhibitor, on laurate-induced peripheral arterial disease in rats was compared with those of prostaglandin E 1 (PGE 1 ), beraprost, and clopidogrel. YM-254890 inhibited ADP-induced ex vivo rat platelet aggregation at a dose of 3 μg/kg. Furthermore, YM-254890 strongly inhibited phenylephrine-, serotonin- and endothelin-1-induced contractions in the rat aorta, and improved dermal blood flow after the laurate injection. The intra-arterial single bolus administration of YM-254890 15 min after the laurate injection dose-dependently inhibited the progression of the lesion, with significance, at 3 μg/kg without affecting systemic blood pressure. PGE 1 and beraprost, when administered before the laurate injection, were effective, but their potencies were less than that of YM-254890. Clopidogrel significantly suppressed lesion progression when administered at 30 mg/kg twice a day for 3 days, which completely inhibited platelet aggregation. These results suggest that the local administration of YM-254890 may be useful for treating peripheral arterial disease.