KETANSERIN REDUCES GRAFT ARTERIOSCLEROSIS AFTER ALLOGENEIC AORTA TRANSPLANTATION IN RATS

The serotonin-2 receptor antagonist ketanserin has been suggested to d iminish arteriosclerotic development by its effect on platelet functio n and on vascular smooth muscle cells. We investigated the ability of ketanserin in reducing immune-mediated arteriosclerosis using the BN-W AG and WAG-BN rat aortic transplantation models. Ketanserin (10 mg/kg/ day) administered in drinking water significantly reduced posttranspla nt arteriosclerotic thickening of the intima in the BN-WAG rat model t o 102 +/- 23 mu m as compared with 171 +/- 60 mu m in untreated BN-WAG allografts 8 weeks posttransplantation (p < 0.05). In the opposite WA G-BN combination, at 4 weeks posttransplantation, no significant reduc tion in intimal thickening was attained (112 +/- 42 vs. 152 +/- 49 mu m). Platelet aggregation to increasing amounts of collagen did not sho w a correlation between the effect of ketanserin on platelet function and reduction in intimal thickening. Ketanserin had no effect on systo lic blood pressure or mononuclear cell infiltration. We conclude that ketanserin reduces graft arteriosclerosis by a mechanism other than by inhibition of platelet function, decrease in blood pressure, or immun osuppression. Because of this antiarteriosclerotic effect, ketanserin therapy might be beneficial to the long-term survival of vascular allo grafts.