n-3 polyunsaturated fatty acids supplementation decreases asymmetric dimethyl arginine and arachidonate accumulation in aging spontaneously hypertensive rats.
BACKGROUND
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.


OBJECTIVE
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 spectrophotometrically in the kidney from each rat.


RESULTS
Animals 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 microM) than OLIVE (0.23 +/- 0.08 microM).


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 highly predictive cardiovascular risk factor.
Raimondi
Laura
L
Dept. of Pharmacology, University of Florence, Florence, Italy. laura.raimondi@unifi.it
Lodovici
Maura
M
Visioli
Francesco
F
Sartiani
Laura
L
Cioni
Laura
L
Alfarano
Chiara
C
Banchelli
Grazia
G
Pirisino
Renato
R
Cecchi
Enrica
E
Cerbai
Elisabetta
E
Mugelli
Alessandro
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000517:prevention & control; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012307:Risk Factors
D015525:Fatty Acids, Omega-3; C487735:dimethylarginine; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D001120:Arginine; D015118:Eicosapentaenoic Acid