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Eicosapentaenoic Acid Stimulates Nitric Oxide Production And Decreases Cardiac Noradrenaline In Diabetic Rats
Author(s) -
Nishimura Masato,
Nanbu Akira,
Komori Toshiaki,
Ohtsuka Ken,
Takahashi Hakuo,
Yoshimura Manabu
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03311.x
Subject(s) - medicine , endocrinology , eicosapentaenoic acid , streptozotocin , nitric oxide , excretion , diabetes mellitus , chemistry , fatty acid , polyunsaturated fatty acid , biochemistry
SUMMARY 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 NO 3 – , 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 NO 3 – excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA‐E. 3. Urinary NO 3 – 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 μmol/g per day, respectively ( P < 0.01); week 6: 279±83 vs 73±9 μmol/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 NO 3 – 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.