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Flavonoids are ingested with vegetables and beverages and exert a beneficial effect on cardiovascular disease. Studies in animals in vitro and in humans ex vivo on the resistance of lipoproteins to oxidation are not consistent and the mechanisms by which flavonoids protect against atherosclerosis are a matter of debate. In the present study, we investigated the effects of administering diets containing 0.3% (wt/wt) quercetin, 0.3% (wt/wt) catechin, or 35% (vol/wt) dealcoholated red wine (DRW) for 10 days in healthy rats on markers of oxidative damage in lipoproteins and in plasma. The antioxidant levels in low-density lipoproteins (LDL) or the lag phase, oxidation rate, and maximum level of conjugated dienes during ex vivo LDL oxidation did not differ between control and treated rats. Plasma levels of [alpha]-tocopherol and retinol were similar in all groups. The total antioxidant status of the plasma from rats fed either quercetin or DRW diet was higher than in control rats. Only glucuronide and sulfate compounds of quercetin were detected in plasma from rats fed the quercetin-rich diet, and no flavonoids or their metabolites were detected in plasma or LDL from rats fed the catechin- or the DRW-rich diet. No significant differences in malondialdehyde or in conjugated dienes in plasma were observed. These results indicate that although metabolites from quercetin are present in plasma, they are not detected in lipoproteins and do not modify the level of other antioxidants. In conclusion, in the absence of any pathology or of oxidative stress the intake of quercetin, catechin, or DRW did not protect lipoproteins from oxidation ex vivo. quercetin; catechin; wine; antioxidants; atherosclerosis

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 ([O.sub.2.sup.-]*) production and related antioxidant activities were also studied in aortic segments. The aortic content of eNOS mRNA was increased in rats ted 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 u-arginine decreased by 30%. No change in aortic [O.sub.2.sup.-]* 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

We examined in vitro the source and role of basal nitric oxide (NO) in proxireal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor [N.sup.G]-nitro-L-arginine methyl ester (LNAME, [10.sup.-4] M), the neuronal blocker tetrodotoxin (TTX, [10.sup.-6] M), or both on spontaneous contractions and on the production of basal NO. Both L-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by L-NAME and was inhibited by 38% by TTX. When tested together, L-NAME in the presence of TTX or TTX in the presence of L-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown. longitudinal smooth muscle; cecum; nonadrenergic, noncholinergic innervation; tetrodotoxin; electron paramagnetic resonance

To study the effect of the degree of unsaturation of dietary fatty acids on the production of free radicals and on the vascular smooth muscle tone in rings of the aorta, Sprague-Dawley rats were fed a semipurified diet containing 5% lipids from either corn oil (CO) or menhaden oil (MO) for 8 wk. The MO diet did not change the basal or NADPH-dependent superoxide anion ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) release. There were no significant differences in phenylephrine-induced contractions between the two groups in intact rings. However, these contractions increased in endothelium-intact aortic rings from the MO group after addition of the nitric oxide ([multiplied by]NO) synthase inhibitor [N.sup.G]-nitro-L-arginine and in endothelium-denuded rings, both indicating a greater endothelial basal [multiplied by]NO production in rats fed with the MO diet. Endothelium-dependent relaxations in response to acetylcholine were more prominent in rings from the MO group. These differences were not due to an increased smooth muscle response to [multiplied by]NO, because relaxations were the same using an exogenous [multiplied by]NO donor. Our results indicate that dietary MO did not modify [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] release by the vessel wall or relaxation due to the cyclooxygenase pathway, but it potentiated endothelial production of [multiplied by]NO. corn oil; polyunsaturated fatty acids; nitric oxide; superoxide anion