Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function

Objectives To determine whether synthetic peptides containing the arginine-glycine-aspartate (RGD) sequence inhibit equine platelet function. Animals For in vitro studies of blood, 3 healthy Thoroughbreds; for in vivo and ex vivo studies of administration of RGD-containing peptides, 4 young adult pony mares. Procedure Blood was incubated with and without addition of aspirin or RGD-containing peptides (RGDS, RPR 110885) and platelet aggregation responses and platelet adhesion to subendothelial collagen were determined. RPR 110885 was administered IV, and platelet function was evaluated. Platelet aggregation was determined by a turbidimetric method, and platelet adhesion was evaluated by the Baumgartner perfusion method. RPR110885 was administered IV at dosages of 30 and 60 μg/kg of body weight, and bleeding time, platelet aggregation responses, and platelet count were determined at hourly intervals for 4 hours. Results Both RGDS and RPR 110885 inhibited platelet aggregation in vitro in dose-dependent manner and inhibited platelet adhesion to subendothelial collagen. The concentration of RGDS that inhibited platelet aggregation by 50% (IC50) was 100 to 142 μM for the various agonists tested, whereas the concentration of RPR 110885 that inhibited platelet aggregation by 50% was 0.03 to 0.05 μM. When administered to ponies at 30 or 60 g/kg, RPR 110885 almost completely inhibited ADP-induced platelet aggregation. Conclusions RGDS and RPR 110885 inhibited equine platelet function; however, RPR 110885 was several thousand times more potent than RGDS. Clinical Relevance RGD-containing peptides may be useful for treatment of thrombotic diseases of horses. (Am J Vet Res 1997;58:457–460)