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Upregulation of endothelial nitric oxide synthase in rat aorta after ingestion of fish oil-rich diet

¹Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, E-08028 Barcelona; ³Unitat de Farmacologia, Facultat de Medicina, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, E-08026 Barcelona; and ²Centre d’Investigacions en Bioquímica i Biologia Molecular, Hospital Vall d'Hebron, E-08035 Barcelona, Spain

Submitted 22 December 2003 ; accepted in final form 24 March 2004

A previous study with aortic segments isolated from rats fed a fish oil-rich diet indicated an increase in acetylcholine-induced nitric oxide (·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 ·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 ·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 (O₂^–·) 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%); ·NO production increased by 90%, cGMP levels increased by 100%, and L-arginine decreased by 30%. No change in aortic O₂^–· 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

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