Pharmacological studies of eicosapentaenoic acid ethylester (EPA-E) on high cholesterol diet-fed rabbits

Abstract

The effects of eicosapentaenoic acid ethylester (EPA-E) at daily doses of 3 and 30 mg/kg (p.o.) on vascular lesions and changes in blood components were investigated in rabbits fed with a 1 % cholesterol diet for 12 weeks and partly compared with those given 30 mg/kg/ day (p.o.) of ticlopidine. EPA-E at 30 mg/kg significantly improved the reduction in distensibility of isolated thoracic aorta caused by cholesterol diet feeding. Ticlopidine at 30 mg/kg also showed significant but milder improvement. EPA-E at 30 mg/kg, unlike ticlopidine, tended to lower cholesterol content in the thoracic wall and elastin fraction. Although EPA-E did not act on plasma total cholesterol, HDL-cholesterol and triglyceride contents, it tended to mildly reduce platelet aggregability in response to sodium arachidonate and the increased production of TXA₂-like activity by platelets. In addition, daily doses of 30 mg/kg EPA-E caused a significant increase in plasma and platelet EPA-E contents without any change in docosahexaenoic acid and arachidonic acid contents. From these results, daily administration of EPA-E to cholesterol diet-fed rabbits caused a remarkable improvement of the reduction in distensibility of isolated thoracic aorta. The mechanism of this improvement by EPA-E appears to depend on the protection of elastic fibers from lipid deposition on the vascular wall.