Ethyl Icosapentate Research Articles

Efficacy of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

Efficacy of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

Alteration in plasma docosahexaenoic acid levels following oral administration of ethyl icosapentate to rats

ObjectivesEthyl icosapentate, a prodrug of eicosapentaenoic acid (EPA), has been prescribed to not only hyperlipidemia, but also psychotic patients. We have examined the impact of an orally administered polyunsaturated fatty acid (PUFA), ethyl icosapentate, on the plasma concentrations of seven other types of fatty acids and one metabolite (3-hydroxybutyrate, 3-HB) using rats. Designand Methods: A commercial omega-3 PUFA, EPA, formulation (ethyl icosapentate, Epadel®) was administered orally to Sprague-Dawley rats (15, 50, 100 mg/kg, n = 4–8) and changes in the plasma fatty acid concentrations were investigated by HPLC using fluorescence detection. ResultsThe concentration of an n-3 PUFA, docosahexaenoic acid (DHA), was significantly increased from 11.6 ± 1.45 (0 h) to 25.9 ± 6.54 μM (6 h) in rat plasma (n = 8, p = 1.88 × 10-2) at a dose of 100 mg/kg, as was the EPA concentration from 2.58 ± 0.16 (0 h) to 6.03 ± 2.20 μM (1 h) (n = 8, p = 2.09 × 10-2), whereas concentrations of other fatty acids, such as α-linolenic acid, palmitoleic acid, arachidonic acid, linolenic acid, and oleic acid, were not significantly changed. In addition, the concentration of the ultimate fatty acid metabolite, 3-hydroxybutyrate (3-HB), was significantly increased (from 94.6 ± 10.2 to 217 ± 43.4, p = 5.41 × 10-3) 12 h after oral administration of ethyl icosapentate (n = 8, 100 mg/kg). ConclusionsThis result suggests that intake of the EPA formulation contributed not only to an increase in EPA concentration, but also to increases in DHA and 3-HB concentrations in vivo.

Effects of Rosuvastatin Add-on Treatment on Hyperlipidemia in Non-diabetic Patients with Nephrotic Syndrome Receiving Ethyl Icosapentate

Effects of Rosuvastatin Add-on Treatment on Hyperlipidemia in Non-diabetic Patients with Nephrotic Syndrome Receiving Ethyl Icosapentate

Effects of rosuvastatin add-on treatment on hyperlipidemia in type 2 diabetic patients with chronic kidney disease receiving ethyl icosapentate

Aim: The frequency of hyperlipidemia is high in diabetic patients, but medications are limited for controlling lipid abnormalities when chronic renal disease (CKD) advances. We evaluated the effects of rosuvastatin, one of the strong statins, on hyperlipidemia in type 2 diabetic patients receiving ethyl icosapentate (EPA).

MP77-02 THE ANTITHROMBOTIC AGENTS DO NOT NEED TO DISCONTINUE PRIOR TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY: A SINGLE CENTER EXPERIENCE.

You have accessJournal of UrologyProstate Cancer: Detection and Screening VI1 Apr 2015MP77-02 THE ANTITHROMBOTIC AGENTS DO NOT NEED TO DISCONTINUE PRIOR TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY: A SINGLE CENTER EXPERIENCE. Kuniaki Tanabe, Yasuhiro Maki, Kyoko Koike, Hirohito Kobayashi, Takashi Arai, Yukihiro Kondo, Tomotaka Hattori, and Naoki Kawamura Kuniaki TanabeKuniaki Tanabe More articles by this author , Yasuhiro MakiYasuhiro Maki More articles by this author , Kyoko KoikeKyoko Koike More articles by this author , Hirohito KobayashiHirohito Kobayashi More articles by this author , Takashi AraiTakashi Arai More articles by this author , Yukihiro KondoYukihiro Kondo More articles by this author , Tomotaka HattoriTomotaka Hattori More articles by this author , and Naoki KawamuraNaoki Kawamura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.542AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES According to the American College of Chest Physicians evidenced-based clinical practice guideline, the risk of thromboembolic complications may be higher with discontinuation of antithrombotic agents (AAs). Although some reports showed that the continuing of AAs such as low-dose aspirin, and warfarin at prostate biopsy may not be associated with increase in risk for bleeding complications which require further interventions, there is no sufficient evidence. Besides, the risk of bleeding events with other AAs such as clopidogrel, ticlopidine, and more drugs has not evaluated yet. We assessed the risk of bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy without discontinuation all AAs. METHODS We retrospectively studied 1621 patients who underwent TRUS-guided prostate biopsy from June 2006 to December 2013. The TRUS-guided prostate biopsy technique is basically standardized 6 to 12 cores from peripheral and transitional zone. We assessed the complications whether some treatments were needed just after biopsy, and we asked about hematuria, rectal bleeding, and haematospermia 2 weeks after biopsy. 298 patients were administrated AAs (group 1) and did not stop those drugs during the procedure. We compared group 1 patients with 1323 patients who were not administrated AAs (group2). RESULTS AAs included warfarin, aspirin, cilostazol, clopidogrel, ethyl icosapentate, sarpogrelate, ticlopidine, dabigatran, and limaprost alfadex. Group 1 patients were administrated 1 to 4 kinds of these drugs. The incidence of bleeding events which were needed some treatments was 4.36% and 1.89% in group 1 and 2 (p=0.011). Only one patient needed transfusion in group2. The incidence of hematuria was 22.6% in group 1, and 16.7% in group2 (p=0.467). The incidence of rectal bleeding was 5.3% and 3.9% respectively (p=0.263). Haematospermia was seen only 0.67% and 1.59% in group 1 and 2. CONCLUSIONS The risk of bleeding complication which needed some treatment after biopsy in the group of patients taking AAs was slightly increased, but statistically insignificant. Furthermore, those events did not affect the hospitalization. There was not any difference concerning the incidence of hematuria, rectal bleeding, and haematospermia between two groups. These results suggest that if some treatment can be performed immediately against the bleeding complication, it is not necessary to discontinue all AAs before TRUS-guided prostate biopsy © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e992 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kuniaki Tanabe More articles by this author Yasuhiro Maki More articles by this author Kyoko Koike More articles by this author Hirohito Kobayashi More articles by this author Takashi Arai More articles by this author Yukihiro Kondo More articles by this author Tomotaka Hattori More articles by this author Naoki Kawamura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The NMatrix, a new method of presenting statistics, displays the characteristics of medicines with similar effects used in the treatment of lumbar spinal stenosis concisely and clearly, facilitating the selection of appropriate medications

BackgroundIt is often difficult to compare the characteristics of a medicine with those of others based on common standards, whereas the application of rational standards would be expected to facilitate the comparison of medicines with similar effects. The present study was conducted to clarify the characteristics of individual medicines and to examine whether rational standards allow the most appropriate medicines to be chosen. MethodsParticipants diagnosed with lumbar spinal stenosis (LSS) were assessed for QOL and ADL based on the Roland–Morris Disability Questionnaire, JOA score, VAS, and the presence of intermittent claudication (IC). Four medicines—beraprost sodium, ethyl icosapentate (EPA), sarpogrelate hydrochloride, and limaprost alfadex (PGE1)—were prescribed in a random manner. These four medicines were assessed independently in four studies using the same study design and size in each case. Using the NMatrix, the characteristics of the four medicines and the results of mutual comparisons could be displayed concisely and clearly in one matrix based on significance levels. This work involved analyzing pooled data from the four studies. ResultsAll four medicines improved IC—one of the characteristic symptoms of LSS—by 12 weeks after administration. PGE1 required more time than the other medicines to affect IC. EPA appeared to almost significantly ameliorate some items at every point, though the evidence was insufficient. ConclusionsThe NMatrix concisely and clearly displays the characteristics of “medicines with similar effects” for the treatment of lumbar spinal stenosis, and can help physicians to choose the optimal medicine based on rational criteria for individual patients, according to their symptoms and progress.

The impact of ethyl icosapentate therapy on coronary fibrous-cap thickness in acute coronary syndrome patients without hyperlipidemia: Assessment by optical coherence tomography study

Backround: It plays important roles to predict vulnerable plaques in patients with acute coronary syndrome (ACS) because the vulnerability of coronary plaques has been relevant to the pathogenesis of ACS. Atheroma with thin-fibrous cap thickness <65 μm estimated by optical coherence tomography (OCT) is thought to be a precursor lesion of plaque rupture. The statin therapy was showed to increase the fibrous cap thickness evaluated by OCT in acute myocardial infarction patients. Recently, several reports have been demonstrated that the intake of fish oil which contained n-3 polyunsaturated fatty acids, including ethyl icosapentate acid (EPA), benefited patients with coronary artery disease clinically. The purpose of study was to examine whether ethyl EPA may have the efficacy to increase in the fibrous-cap thickness similar to statin. Methods: We enrolled consecutive 30 ACS patients fulfilled the following two criteria: (i) LDL-cholesterol <100 mg/dl without statin therapy; and (ii) a non-target lesion with a lipid-rich plaque. They were divided into two groups randomly; the EPA treatment group (n=15) or the control group (n=15). Serial OCT analyses were performed at baseline and nine-month follow-up for a non-PCI lipid-rich plaque lesion. Results: There was no significant difference in patients characteristics and the lipid profile between EPA and control group. Although the fibrous-cap thickness was significantly increased in both the EPA group (169±70μm to 203±53μm, p<0.001) and the control group (175±59μm to 189±61μm, p=0.019) during follow-up period, the relative change in the fibrous-cap thickness from baseline to follow-up of the EPA group was significantly greater than that of the control group (131±32% vs. 108±12%, p=0.017). There was no significant difference in lipid arc from baseline to follow-up in both groups (131±52° to 126±54° vs. 141±49° to 139±50°, p=0.098 vs. 0.485). Conclusion: These findings suggest that EPA treatment is effective in the plaque stabilization with the ACS patients and OCT can help to assess the efficacy of treatment for plaque stabilization.

Successful treatment with low‐dose gemtuzumab ozogamicin in combination chemotherapy followed by stem cell transplantation for children with refractory acute myeloid leukaemia

Successful treatment with low‐dose gemtuzumab ozogamicin in combination chemotherapy followed by stem cell transplantation for children with refractory acute myeloid leukaemia

EFFECT OF ETHYL ICOSAPENTATE THERAPY WITH ASSESSMENT BY OPTICAL COHERENCE TOMOGRAPHY STUDY IN LOW LDL-CHOLESTEROL PATIENTS WITH ACUTE CORONARY SYNDROME

Atheroma with thin-fibrous cap thickness <65 μm estimated by optical coherence tomography (OCT) is thought to be a precursor lesion of plaque rupture. The purpose of study was to examine whether ethyl icosapentate (EPA-E) may have the effect to increase in the fibrous-cap thickness similar to

Aspirin- and Clopidogrel-associated Bleeding Complications: Data Mining of the Public Version of the FDA Adverse Event Reporting System, AERS

Objective: Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the bleeding complications induced by the administration of antiplatelets and to attempt to determine the rank-order of the association.Methods: After a deletion of duplicated submissions and the revision of arbitrary drug names, AERs involving warfarin, aspirin, cilostazol, clopidogrel, ethyl icosapentate, limaprost alfadex, sarpogrelate, and ticlopidine were analyzed. Authorized pharmacovigilance tools were used for the quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.Results: Based on 22,017,956 co-occurrences, i.e., drug-adverse event pairs, found in 1,644,220 AERs from 2004 to 2009, 736 adverse events were listed as warfarin-associated adverse events, and 147 of the 736 were bleeding complications, including haemorrhage and haematoma. Both aspirin and clopidogrel were associated with haemorrhage, but the association was more noteworthy for clopidogrel. As for bleeding complications related to the gastrointestinal system, e.g., melaena and haematochezia, the statistical metrics suggested a stronger association for aspirin than clopidogrel. The total number of co-occurrences was not large enough to compare the association with bleeding complications for the other 5 antiplatelets.Conclusions: The data strongly suggest the necessity of well-organized clinical studies with respect to antiplatelet-associated bleeding complications.

Effect of n-3 Fatty Acid Supplementation on Urinary Risk Factors for Calcium Oxalate Stone Formation

Findings are inconsistent in a few studies of the effect of n-3 fatty acid supplementation on urinary calcium and oxalate excretion in stone formers. We evaluated the physiological effects of supplementation with eicosapentaenoic acid and docosahexaenoic acid on urinary risk factors for calcium oxalate stone formation under standardized conditions. We studied 15 healthy subjects initially while consuming a standardized diet for 5 days (control phase). During consecutive intervention phases 1-5-day standardized diet, 2-20-day free diet and 3-5-day standardized diet participants received 900 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily. While ingesting the standardized diets, daily 24-hour urine samples were collected. After short-term supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 1 we noted no changes in urinary parameters compared to the control phase. After 30-day supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 3 relative supersaturation with calcium oxalate decreased significantly by 23% from a mean ± SD of 2.01 ± 1.26 to 1.55 ± 0.84 due to significantly decreased urinary oxalate excretion (p = 0.023). Other urinary variables were not affected by supplementation. Results show that 30-day n-3 fatty acid supplementation effectively decreases urinary oxalate excretion and the risk of calcium oxalate crystallization. The mechanism of the physiological effect may be decreased cellular oxalic acid exchange attributable to an altered fatty acid pattern of membrane phospholipids with concomitant changes in oxalate transporter activity. Calcium oxalate stone formers may benefit from long-term n-3 fatty acid supplementation.

Successful treatment of lipoprotein glomerulopathy in a daughter and a mother using niceritrol

We report two patients, a daughter and a mother, with lipoprotein glomerulopathy (LPG) who were successfully treated with niceritrol. Both patients carried a mutation in the apolipoprotein E (apoE) gene known as ApoE Tokyo/Maebashi. The daughter was found to have proteinuria at the age of 4 years. Four years later, she was diagnosed as having LPG based on a renal biopsy. She was treated with several medications including pravastatin, ethyl icosapentate, enalapril, warfarin and cyclophosphamide, all of which failed to reduce her proteinuria. At the age of 17 years, she exhibited an increase in proteinuria and a decline in renal function, despite ongoing treatment with pravastatin and enalapril. After switching from pravastatin to niceritrol, a marked reduction in the proteinuria and an improvement in renal function were observed. Her mother was found to have proteinuria at the age of 57 years and was diagnosed as having LPG based on a renal biopsy. She was also treated with niceritrol, resulting in an improvement in her proteinuria and renal function. These cases suggest that niceritrol might be a useful therapeutic option for LPG.

内服薬剤の懸濁液によるポリスチレン製器具の溶解現象―薬剤の懸濁に用いる器具の材質への注意―

Epadel S®,a seamless capsule form of ethyl icosapentate (EPA-E),was made into a suspension in 20 ml of hot water (55°C) and stirred with a polystyrene (PS) disposable spoon.When left in the suspension,the surface of the spoon started to dissolve after 45 minutes,and was completely dissolved after 12 hours.We also investigated the dissolution of PS utensils in suspensions made from teprenone (Selbex®) capsules or powder,or gefarnate (Gefanil®) capsules.Up till now,there have been no reports of toxicity due to PS or the non-reactants and/or by-products produced in the PS production process.However,as the dissolution of spoons,cups or other common utensils made of PS in drug suspensions could cause concern among patients,caregivers,and medical staff,it is important to instruct them to avoid the use of such utensils when preparing drug suspensions.

コレスチミド服薬による血糖コントロール改善効果が確認できた家族性高コレステロール血症合併2型糖尿病の1例

A 65-year-old woman had been treated for type 2 diabetes mellitus, familial hypercholesterolemia and old myocardial infarction. Combination therapy of atorvastatin (40 mg/day), ethyl icosapentate (1,200 mg/day), probucol (500 mg/day) and colestimide (1 g/day) had never reached an ideal low-density lipoprotein cholesterol (LDL-C) level. However the conversion to high dose of colestimide (4 g/day) with the same dose of atorvastatin, ethyl icosapentate, and probucol obviously decreased her LDL-C level from 181.2 mg/dl to 148 mg/dl. Reduction of LDL-C level was also associated with the lowering of glycohemoglobin A1c from 10.7% to 8.7% simultaneously. Challenge tests by the cessation and resumption of only colestimide treatment clearly indicated that colestimide has both cholesterol and blood glucose lowering effect. Her body weight and appetite did not change by colestimide treatment. We think that colestimide therapy might provide a beneficial effect on atherosclerotic disease in diabetes mellitus with dyslipidemia through reduction of cholesterol and blood glucose.

Diacylglycerol oil for apolipoprotein C-II deficiency

Sir, Apolipoprotein C-II is a cofactor of lipoprotein lipase (LPL), which hydrolyses triglycerides of chylomicrons and very low-density lipoproteins (VLDLs).1 We report our therapeutic experience with diacylglycerol (DAG) oil, a natural edible oil, in a patient with apolipoprotein C-II deficiency, a rare, autosomal, recessively-inherited disease. A 43-year-old Japanese man presented with hypertriglyceridaemia, chylomicronaemia, hepatosplenomegaly, postprandial epigastric pain, and recurrent attacks of pancreatitis. Fasting serum triglyceride fluctuated from 545 to 2252 mg/dl, even on treatment with fibrate and ethyl icosapentate, indicating refractory hypertriglyceridaemia. On admission, levels of fasting serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, plasma glucose, and haemoglobin A1c were 317, 33, 28, 2252, 107 mg/dl and 5.0%, respectively. Serum apolipoprotein …

Ethyl icosapentate (omega-3 fatty acid) causes accumulation of lipids in skeletal muscle but suppresses insulin resistance in OLETF rats

Ethyl icosapentate (EPA) is known to improve insulin resistance in non–insulin-dependent diabetes mellitus (NIDDM); however, its mechanism is unclear. In this study, we attempted to determine the mechanism of EPA's effects on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Administration of EPA caused a reduction in plasma cholesterol and triglycerides, but increased cholesterol and triglyceride contents in skeletal muscle. EPA did not have an effect on glucose or insulin levels. EPA accelerated the glucose infusion rate (GIR) and improved the endothelium-dependent relaxation of OLETF rat the thoracic aorta caused by addition of acetylcholine. However, the improvement observed in endothelium-dependent relaxation disappeared after addition of Nw-nitro-L-arginine (L-NA). Furthermore, when L-NA and indomethacine were added to the medium, relaxation of the aorta in EPA-treated rats was weaker than that in control rats. These actions may cause NO induction in the endothelium and an increase in prostaglandin I2 (PGI2) and prostaglandin I3 (PGI3) action, which in turn may result in improvement of insulin resistance. Copyright 2003, Elsevier Science (USA). All rights reserved.

Assessment of antithrombotic agents using the platelet aggregation test

Background: A number of antithrombotic agents are available for use in patients with arteriosclerotic disease. However, no guidelines have been established for their clinical use. Objective: The purpose of this study was to compare the ability of various antithrombotic agents to inhibit experimentally induced platelet aggregation. Methods: Sixteen angina-free patients who had undergone coronary artery bypass surgery >6 months before the start of this trial were studied. After a 4-week washout period, ticlopidine hydrochloride (TIC) 400 mg/d, dipyridamole (DIP) 300 mg/d, cilostazol (CIL) 200 mg/d, trapidil 300 mg/d, beraprost sodium 120 μg/d, aspirin dialuminate (ASP) 81 mg/d, ethyl icosapentate 1800 mg/d, and sarpogrelate hydrochloride (SAR) 300 mg/d were administered orally in sequence for 4 weeks each, and platelet aggregation activity was determined at the end of each 4-week period. There were no washout periods between medications. Adenosine diphosphate (ADP) 2, 5, and 10 μmol/L; arachidonic acid 2 mmol/L; and collagen 2 μg/mL were used as agonists. Results: Medication was discontinued in 5 patients—2 patients while receiving DIP, 2 while receiving CIL, and 1 while receiving SAR—due to subjective symptoms. TIC suppressed platelet aggregation significantly at all 3 doses of ADP ( P < 0.01) and with arachidonic acid ( P < 0.01); ASP with ADP 5 and 10 μmol/L ( P < 0.05), arachidonic acid ( P < 0.01), and collagen ( P < 0.01); and CIL with ADP 2 μmol/L ( P < 0.01) and arachidonic acid ( P < 0.01). A marked inhibition of platelet aggregation, as measured by the platelet aggregation test used in this study, was seen with TIC (maximum mean aggregation 66.8% reduced to 34.0% with ADP 5 μmol/L as the agonist), with CIL (72.4% reduced to 29.7% with arachidonic acid as the agonist), and with ASP (72.4% reduced to 3.0% with arachidonic acid as the agonist). Conclusions: These results show that TIC, ASP, and CIL, but not the other 5 agents studied, had a significant antithrombotic effect in this sample of patients, as measured by the platelet aggregation test.

Effect of ethyl icosapentate on urinary calcium and oxalate excretion.

The effect of ethyl icosapentate (EPA-E) on urinary calcium and oxalic acid excretion was examined to evaluate whether EPA-E is useful in the prevention of calcium-containing urinary stones. For 6 months, urine was measured daily from 40 calcium-containing urinary stone producers at an outpatient clinic, before and after the administration of 1800 mg/day EPA-E. The urine was measured for volume, urea nitrogen, creatinine, calcium, magnesium, phosphorus, uric acid, oxalic acid and citric acid. Serum total cholesterol and triglyceride were also measured. Urinary calcium excretion was not reduced in any of the patients or particular hypercalciuric groups, nor did the level of calcium change. However, nine of the 25 hypercalciuric patients experienced a significant urinary calcium reduction to the normal calciuric level (a reduction of approximately 44%). It is not known why these particular patients experienced a reduction. Urinary oxalic acid did not change, whether hypercalciuria was present or not. These findings suggest that EPA-E is not particularly effective in reducing urinary calcium excretion in the hypercalciuric patients, but it needs future investigation because some patients experienced significant urinary calcium reduction.

Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women

Objective: To assess the efficacy and safety of eicosapentaenoic acid for the treatment of hyperlipidemia in symptomatic menopausal Japanese women. Methods: We performed a prospective observational 48-week study in hyperlipidemic menopausal women. We randomly assigned 141 women, whose levels of serum total cholesterol were 220 to 280 mg/dL or whose serum triglycerides were 150 to 400 mg/dL at baseline to groups treated with estriol (E3) 2 mg daily (control group, n = 72) or ethyl icosapentate 1800 mg daily and E3 2 mg (eicosapentaenoic acid group, n = 69). Results: Serum levels of total cholesterol decreased significantly from 249.4 to 238.6 mg/dL (−4.3%, P = .003) in the control group and from 252.3 to 234.0 mg/dL (−7.3%, P = .001) in the study group at week 48 in the women whose total cholesterol was not less than 220 mg/dL at baseline. Serum levels of triglycerides decreased significantly from 194.5 to 141.5 mg/dL (−27.2%, P = .001) in the study group but increased slightly from 192.9 to 207.4 mg/dL (+7.5%) in the control group at week 48 in the women whose level of triglycerides was not less than 150 mg/dL. There were significant differences between these two groups at weeks 12, 24, and 48. Serum levels of total cholesterol and triglycerides were significantly decreased at week 48 in the study group regardless of whether the women were obese. There were no severe adverse effects. Conclusion: Combination therapy with eicosapentaenoic acid and E3 was effective and safe for menopausal women with hypertriglyceridemia.

Eicosapentaenoic acid stimulates nitric oxide production and decreases cardiac noradrenaline in diabetic rats.

1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We measured changes in urinary excretion of NO3-, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of N(G)-nitro-L-arginine (L-NNA), a NO synthase inhibitor, on urinary NO3- excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E. 3. Urinary NO3- excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120+/-8 vs 51+/-11 micromol/g per day, respectively (P<0.01); week 6: 279+/-83 vs 73+/-9 micromol/g per day, respectively (P<0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3- and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.