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.
Nishimura
M
M
Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan. nishim@labmed.kpu-m.ac.jp
Nanbu
A
A
Komori
T
T
Ohtsuka
K
K
Takahashi
H
H
Yoshimura
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019270:Fructosamine / Q000097:blood; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D009566:Nitrates; D019335:Nitroarginine; D009569:Nitric Oxide; D019270:Fructosamine; D001120:Arginine; D015118:Eicosapentaenoic Acid; D019001:Nitric Oxide Synthase; D009638:Norepinephrine