mdl-100907 and Arteriosclerosis

Sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, is known to prevent serotonin-induced neointimal hyperplasia. We examined the effect of this agent on allograft arteriosclerosis in a rat model of aortic transplantation.. Rats were given an aortic isograft or allograft and oral administration of either saline vehicle alone or 20mg/kg daily of sarpogrelate for 8 weeks. The grafts were then harvested, and the lumen diameter and the thickness of the intima and media were measured. Comparisons were made between measurement results in isografts and allografts from rats treated and not treated with sarpogrelate. Immunohistochemistry assessments were used to detect expression of serotonin in graft specimens.. For both allografts and isografts, significantly less intimal thickening was observed in specimens from rats given sarpogrelate compared with rats given saline. Sarpogrelate had no effect on medial thickening in either graft type. Serotonin was detected in allografts from rats given saline alone but not in allografts from rats given sarpogrelate or in isografts.. Sarpogrelate hydrochloride may mitigate arteriosclerosis in allografts. Platelet aggregation and serotonin may be correlated with intimal thickening associated with chronic rejection.

Topics: Allografts; Animals; Aorta; Arteriosclerosis; Fibrinolytic Agents; Male; Organ Transplantation; Rats; Rats, Inbred Lew; Serotonin 5-HT2 Receptor Antagonists; Succinates

Early microvascular constriction following atherosclerotic plaque rupture may be mediated via serotonin and/or endothelin-1. Atherosclerotic lesions in the rabbit hindlimb underwent plaque rupture, resulting in a rapid reduction of distal flow (7.1+/-0.7 ml/min pre-rupture versus 3.6+/-0.6 ml/min post-rupture, P<0.001) and a rise in distal microvascular resistance (10.5+/-0.9 mm Hg min/ml pre-rupture versus 23.5+/-3.5 mm Hg min/ml post-rupture, P=0.01). Distal microvascular resistance remained elevated following endothelin-1 receptor antagonism and control vehicle, but normalised after serotonin receptor antagonism with ritanserin (10.5+/-0.9 mm Hg min/ml pre-rupture versus 22.2+/-6.0 mm Hg min/ml post-endothelin-1 receptor antagonism [P<0.05] versus 21.6+/-6.2 mm Hg min/ml post-control vehicle [P<0.05] versus 11.6+/-2.0 mm Hg min/ml post-ritanserin [P=NS]). Early antagonism of serotonin receptors protects against distal microvascular constriction following atherosclerotic plaque rupture.

Topics: Animals; Arteriosclerosis; Blood Flow Velocity; Disease Models, Animal; Iliac Artery; Indans; Microcirculation; Rabbits; Receptors, Serotonin, 5-HT2; Ritanserin; Rupture; Serotonin 5-HT2 Receptor Antagonists; Vasoconstriction