Ketanserin Reduces Graft Arteriosclerosis After Allogeneic Aorta Transplantation in Rats

Abstract

The serotonin-2 receptor antagonist ketanserin has been suggested to diminish arteriosclerotic development by its effect on platelet function and on vascular smooth muscle cells. We investigated the ability of ketanserin in reducing immune-mediated arteriosclerosis using the BN-WAG and WAG-BN rat aortic transplantation models. Ketanserin (10 mg/kg/day) administered in drinking water significantly reduced posttransplant arteriosclerotic thickening of the intima in the BN-WAG rat model to 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 WAG-BN combination, at 4 weeks posttransplantation, no significant reduction in intimal thickening was attained (112 +/- 42 vs. 152 +/- 49 mu m). Platelet aggregation to increasing amounts of collagen did not show a correlation between the effect of ketanserin on platelet function and reduction in intimal thickening. Ketanserin had no effect on systolic 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 immunosuppression. Because of this antiarteriosclerotic effect, ketanserin therapy might be beneficial to the long-term survival of vascular allografts.

A Synergistic Effect of Serotonin Transporter Gene Polymorphism and Smoking in Association with CHD

“…Ketanserin may diminish arteriosclerotic development by affecting platelet and vascular smooth muscle cell functions (5). Ketanserin reduces immune-mediated arteriosclerosis in rat aortic transplantation models (5). These data indicate that serotonin plays a role in the etiology of CHD.…”

“…This vasoconstriction was significantly blunted in patients who received ketanserin, a serotonin 2A receptor antagonist (4). Ketanserin may diminish arteriosclerotic development by affecting platelet and vascular smooth muscle cell functions (5). Ketanserin reduces immune-mediated arteriosclerosis in rat aortic transplantation models (5).…”