Ketanserin reduces graft arteriosclerosis after allogeneic aorta transplantation in rats.
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.
Department of Surgery, Erasmus University, Rotterdam, The Netherlands.
R A
RA
Geerling
R W
RW
de Bruin
M
M
Scheringa
F
F
Bonthuis
J N
JN
IJzermans
R L
RL
Marquet
D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014184:Transplantation, Homologous
D012702:Serotonin Antagonists; D007650:Ketanserin