Omega-3 polyunsaturated fatty acids augment endothelium-dependent vasorelaxation by enhanced release of EDRF and vasodilator prostaglandins.
Dietary supplementation with fish oil results in augmentation of endothelium-dependent vasorelaxation in experimental animals. The present study was designed to evaluate the direct in vitro effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on vascular reactivity in isolated rat aortic rings. Aortic rings were incubated with the omega-6PUFA arachidonic acid (AA, 10(-7) M) or the omega-3 PUFAs eicosapentaenoic acid (EPA, 10(-7) M) and docosahexaenoic acid (DHA, 10(-7) M) in an organ bath at 37 degrees C. Following contraction with norepinephrine, changes in isometric force were measured in response to the endothelium-dependent vasodilators acetylcholine (ACh, 10(-10) to 10(-5) M) or the calcium ionophore A23187 (10(-10) to 10(-5) M). Parallel sets of vascular rings were pretreated with the cyclooxygenase inhibitor indomethacin (10(-5) M) or the inhibitor of nitric oxide synthesis NG-monomethyl L-arginine (L-NMMA 5 x 10(-5) M) prior to treatment with AA or EPA. Treatment of rings with EPA resulted in an increase (P less than 0.05) in ACh-mediated vasorelaxation compared both to AA-treated and buffer-treated rings (maximum relaxation 83 +/- 5% vs 46 +/- 5% and 63 +/- 4%, respectively). A similar augmentation was observed in DHA-treated rings. Pretreatment of rings with indomethacin or I-NMMA decreased (P less than 0.05) the ACh-mediated vasorelaxation, although EPA-treated rings showed less (P less than 0.05) attenuation of ACh response compared to AA-treated or untreated control rings.(ABSTRACT TRUNCATED AT 250 WORDS)
Lawson
D L
DL
Department of Medicine, University of Florida, College of Medicine, Gainesville 32610.
Mehta
J L
JL
Saldeen
K
K
Mehta
P
P
Saldeen
T G
TG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
D015525:Fatty Acids, Omega-3; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin