Abstract 17081: Long-term Administration of Eicosapentaenoic Acid Ameliorates Vascular Endothelial Dysfunction Through the Renin-angiotensin-aldosterone System Inhibition Resulting in the Improvement of Muscle Oxygen Metabolism in Patients With Lifestyle Related Disease

Abstract

Background: Elevated activity of renin-angiotensin-aldosterone system (RAAS) is known to induce vascular endothelial dysfunction in patients with lifestyle related disease such as diabetes mellitus (DM), hypertension (HT) and dyslipidemia (DL). Because the vascular endothelial dysfunction disturbs an appropriate blood flow to skeletal muscles, it is considered that the oxygen metabolism is impaired in them. Although eicosapentaenoic acid (EPA) has been reported to inhibit the RAAS, it is unclear whether EPA ameliorates vascular endothelial dysfunction via the RAAS inhibition resulting in the improvement of muscle oxygen metabolism. This study investigated the effects of EPA on vascular endothelial function and muscle oxygen metabolism during exercise in patients with lifestyle related disease. Methods: Ninety-two patients (68±8 years, 50 males) were divided into two groups based on the EPA administration in crossover method, after their DM, HT and/or DL were optimally treated. When patients took 1,800 mg of EPA daily for 8 months or not, they were in the EPA(+) group or in the EPA(-) group. In the end of each treatment period, cardiopulmonary exercise test was performed to measure oxygen uptake (VO 2 ) at anaerobic threshold (VO 2 AT ), peak VO 2 and the time from the start of the test to the AT (Time AT ) and endpoint (Time EP ). We measured serum EPA, plasma renin activity (PRA), aldosterone (ALD), adrenalin (ADRN) and noradrenalin (NORA), and reactive hyperemia index (RHI). We used the changes in PRA, ALD, ADRN and NORA before and after a cycle ergometer exercise test (ΔPRA, ΔALD, ΔADRN and ΔNORA) as neurohumoral factors, RHI as a parameter of vascular endothelial function and Time EP as an exercise capacity. Results: There were no significant differences in ΔPRA, ΔALD, ΔNORA, peak VO 2 and Time EP between the two groups. The PRA, ALD and ΔADRN were significantly lower in the EPA(+) group than in the EPA(-) group (P<0.05, respectively). The RHI, VO 2 AT and Time AT were significantly higher in the EPA(+) group than in the EPA(-) group (P<0.05, respectively). Conclusion: Long-term administration of EPA ameliorated vascular endothelial dysfunction via the RAAS inhibition resulting in the improvement of muscle oxygen metabolism in lifestyle related disease patients.