EFFECT OF PLATELET-ACTIVATING-FACTOR (PAF) RECEPTOR BLOCKERS ON SMOOTH-MUSCLE CELL REPLICATION IN-VITRO AND ALLOGRAFT ARTERIOSCLEROSIS IN-VIVO

Platelet-activating factor (PAF) stimulates smooth muscle cell (SMC) r eplication both in vivo and in vitro. In this study we have investigat ed whether PAF receptor-blocking molecules modulate SMC replication in vitro and the generation of allograft arteriosclerosis in vivo. SMC c ultures were established from baby rat aorta media and fibroblast cont rol cultures from the adventitia. Identification of the cultured cell types was determined both by immunohistochemistry and electron microsc opy. Both cell types replicated in culture with 10% fetal calf serum ( FCS). The addition of PAF-C18 enhanced, and the addition of three PAF receptor inhibitors - WEB 2086, WEB 2170, and BN 50739 - reduced, SMC replication and protein synthesis in a dose-dependent fashion in vitro until toxic concentrations were reached. The most potent of these dru gs, WEB 2170, was then delivered at the rate of 12 mg/kg per day to re cipients of rat aortic allografts. The responses were quantitated by a utoradiography after short-term labeling of the recipients with tritiu m-labeled thymidine (H-3-TdR) and by quantitative morphology. Administ ration of the PAF receptor blocker had no impact on the replication of the inflammatory cells in the allograft adventitia nor on the replica tion of SMCs in the media and intima. Administration of the PAF recept or blocker delayed the generation of allograft arteriosclerosis slight ly, but not significantly. These results suggest that PAF is not an es sential component in the inflammatory cascade leading to allograft art eriosclerosis.