[Pharmacological studies of eicosapentaenoic acid ethylester (EPA-E) on high cholesterol diet-fed rabbits].
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.
Mizota
M
M
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Katsuki
Y
Y
Mizuguchi
K
K
Endo
S
S
Miyata
H
H
Kojima
M
M
Kanehiro
H
H
Okada
M
M
Takase
A
A
Ishiguro
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D001792:Blood Platelets / Q000187:drug effects; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D011817:Rabbits
D002791:Cholesterol, Dietary; D008055:Lipids; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid