Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice.
BACKGROUND
Eicosapentaenoic acid (EPA) is thought to have many beneficial effects, such as anti-atherosclerogenic and anti-inflammatory properties. However, few studies have reported its effects of endothelial dysfunction in diabetes and its direct effects on the aorta. Here, we investigated the effects of EPA treatment on impaired endothelium-dependent relaxation of the aorta in KKAy mice, a model of type 2 diabetes.


METHODS
Male KKAy mice were fed a high-fat (HF) diet for 8 weeks to induce diabetes, after which they were divided into two groups. One group was fed a HF diet, and the other group was fed a HF diet containing EPA ethyl ester (EPA-E, 10 mg/day) for 4 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if EPA-E administration changed vascular function in these diabetic mice. In addition, we examined effect of EPA-E and its metabolites to vascular action using aorta separated from C57BL/6 J mice.


RESULTS
Although EPA-E administration did not change the plasma glucose and insulin levels in diabetic mice, total cholesterol levels were significantly decreased. The aorta extracted from EPA-E untreated diabetic mice showed impaired endothelium-dependent relaxation in response to acetylcholine (ACh). However, EPA-E administration improved the relaxation response to ACh to the control levels observed in non-diabetic C57BL/6 J mice. On the other hand, endothelium-independent relaxation in response to sodium nitroprusside did not significantly differ among these three groups. The enhanced contractile response by phenylephrine in diabetic mice was not altered by the administration of EPA-E. In addition, the direct administration of EPA-E metabolites such as EPA, docosahexaenoic acid, and docosapentaenoic acid led to vasodilation in the aortic rings of C57BL/6 J mice.


CONCLUSION
These results showed that chronic EPA-E administration prevented the development of endothelial dysfunction in KKAy mice, partly via the direct action of EPA-E metabolites on the aorta.
['Takenouchi|Yasuhiro|Y|', 'Ohtake|Kazuo|K|', 'Nobe|Koji|K|', 'Kasono|Keizo|K|']
D000109:Acetylcholine D000818:Animals D001013:Aorta, Thoracic D001786:Blood Glucose D002317:Cardiovascular Agents D002784:Cholesterol D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D059305:Diet, High-Fat D015118:Eicosapentaenoic Acid D004730:Endothelium, Vascular D007328:Insulin D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D009119:Muscle Contraction D009599:Nitroprusside D010656:Phenylephrine D046509:Tissue Culture Techniques D014664:Vasodilation
Eicosapentaenoic acid Diabetes Endothelium Thoracic aorta