n-3 polyunsaturated fatty acid supplementation reduces asymmetric dimethylarginine and arachidonate accumulation in spontaneously hypertensive rats

Plasma accumulation of asymmetric dimethyl arginine (ADMA), is considered as a risk factor for endothelial dysfunction and a strong predictor for coronary heart diseases. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) increasing plasma levels have been positively associated with reduced cardiovascular mortality with a mechanism(s) yet unclear.We hypothesised that ADMA reduction might be a part of EPA and DHA beneficial effects on the cardiovascular system. Aim To verify this hypothesis we measured ADMA plasma levels in aged spontaneously hypertensive rats (SHR) supplemented for 8 weeks with EPA and DHA. Methods 16-month-old SHR were supplemented with EPA and DHA (EPA-DHA) or with olive oil (1 g/kg/day; OLIVE).At the end of the treatments, the plasma of each animal was analysed for 1) the total fatty acid composition, by gas-cromatography, 2) ADMA levels, by high pressure liquid chromatography, 3) nitrite and homocysteine concentration by chemiluminescence and by polarisation immunoassay respectively.Moreover, the activity of dimethyl arginine dimethyl amino hydrolase, the main enzyme involved in ADMA metabolism, was measured pectrophotometrically in the kidney from each rats. Results Animal supplemented with EPA and DHA showed: 1) lower ADMA and arachidonate plasma levels (587.4±113.7 nM and 0.49±0.11 mM respectively) than the values found in OLIVE rats (1365±399 nM and 1.07±0.07 mM respectively) 2) higher nitrite content (0.73±0.05 μM) than OLIVE (0.23±0.08 μM) Conclusions EPA and DHA supplementation reduced ADMA accumulation in SHR in parallel with a decrease of arachidonate availability. This finding suggests that the control of the inflammatory ground of endothelium might play an important role in EPA and DHA effect on this novel and high predictive cardiovascular risk factor.