López, Diego, Xavier Orta, Kelly Casós, M. Puy Sáiz, Pere Puig-Parellada, Mireia Farriol, and M. Teresa Mitjavila. Upregulation of endothelial nitric oxide synthase in rat aorta after ingestion of fish oil-rich diet. Am J Physiol Heart Circ Physiol 287: H567-H572, 2004. First published April 1, 2004; 10.1152/ajpheart.01145.2003.-A previous study with aortic segments isolated from rats fed a fish oil-rich diet indicated an increase in acetylcholine-induced nitric oxide ( ⅐ NO)-mediated relaxation. However, it remained to be elucidated whether a fish oil-rich diet affects the vascular activity per se and the point of the ⅐ NO-cGMP pathway at which fish oil acts. For this purpose, two groups of Sprague-Dawley rats were fed a semipurified diet containing 5% lipids, either corn oil (CO) or menhaden oil (MO), for 8 wk. We studied the mRNA and protein levels of endothelial NO synthase (eNOS) and NOS activity. The bioavailability of vascular ⅐ NO was assessed directly by electron spin resonance spectroscopy. The levels of cGMP, L-arginine, and L-citrulline were also evaluated in homogenates. Superoxide anion (O 2 Ϫ ⅐ ) production and related antioxidant activities were also studied in aortic segments. The aortic content of eNOS mRNA was increased in rats fed the MO-rich diet. This resulted in increases in both eNOS protein levels (70% relative to the rats fed the CO-rich diet) and NOS activity (102%); ⅐ NO production increased by 90%, cGMP levels increased by 100%, and L-arginine decreased by 30%. No change in aortic O 2 Ϫ ⅐ production was caused by dietary MO. The upregulation of the eNOS-cGMP pathway induced by dietary MO may contribute to the maintenance of vascular homeostasis and explain its beneficial effect in the prevention of arterial diseases. polyunsaturated fatty acids; endothelium; nitric oxide; superoxide anion; free radicals FISH AND FISH OILS are the main source of human dietary long-chain -3 polyunsaturated fatty acids. A fish oil-rich diet performs multifaceted actions (8). It replaces arachidonic acid by eicosapentanoic acid (20:5-3) and docosahexanoic acid (22:6-3) in phospholipid membranes (34, 36), induces changes in eicosanoid metabolites, and impairs free radical release in different types of stimulated cells (6,7,22,37,43).It is widely accepted that damage to the endothelium plays a key role in the development of early atherosclerosis and that fish oils prevent atherosclerosis (10,14) and significantly improve endothelial function in hypercholesterolemic subjects (44). The accumulation of oxidized lipids in the vascular wall suggests that free radical-mediated tissue injury may be a focal point in the formation of atherosclerotic lesions (12, 23). However, nitric oxide (⅐NO) has been described as essential for the regulation of vascular tone and hemodynamics (13), and ⅐NO also displays antiatherogenic properties both in vivo (31) and in vitro (21). We previously found (18) that a fish oil-rich diet increases the acetylcholine-mediated relaxation of rat aortic segments. This increase is due neit...

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