We investigated the antihypertensive effect of lutein on NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3±9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434±26 to 376±33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

This study was performed to investigate the effects of acteoside on various cellular functions such as, intracellular Ca(2+) mobilization, phospholipase C activity, and exocytosis induced by melittin. Melittin (0.1-1 μM) dose-dependently increased intracellular Ca(2+) mobilization in the presence of extracellular Ca(2+), but was not affected by 1 μM U73122, a specific PLC inhibitor. In the absence of extracellular Ca(2+), melittin (1 μM) did not induce a change in intracellular Ca(2+) mobilization, which suggests that melittin-induced intracellular Ca(2+) mobilization may be dependent on the influx of extracellular Ca(2+) rather than on the release of intracellular Ca(2+) storage. Acteoside (10 μM) significantly inhibited 1 μM melittin-induced Ca(2+) mobilization by 33 %. In [(3)H]inositol-labeled cells, 1 μM melittin did not increase inositol phosphate formation, but more than 5 μM melittin significantly increased inositol phosphate formation, which was significantly inhibited by acteoside. Melittin (1 μM) significantly increased histamine release from RBL 2H3 cells in the presence or absence of extracellular Ca(2+). Acteoside significantly inhibited 1-μM-melittin-induced histamine release by 74 % in the presence of extracellular Ca(2+) and by 71 % in the absence of extracellular Ca(2+). These data suggest that the inhibitory effect of acteoside on 1 μM-melittin-induced histamine release may be related to blockage of the calcium-independent pathway. Taken together, these data suggest that melittin has an influence on cellular functions such as intracellular Ca(2+) mobilization, the PLC pathway, and exocytosis via various independent signalling pathways in RBL-2H3 cells, and was significantly inhibited by acteoside.

To investigate the inhibitory effect of acteoside on the process of exocytosis induced by melittin, we measured Ca(2+) mobilization, arachidonic acid (AA) release and catecholamine exocytosis in PC12 chromaffin cells. Melittin significantly increased the intracellular Ca(2+) mobilization via receptor-operated calcium channel but not the intracellular Ca(2+) release. It caused AA release via activation of Ca(2+)-dependent phospholipase A2 (PLA2) and catecholamine secretion in a dose-dependent manner. Acteoside dose-dependently inhibited the release of AA and intracellular Ca(2+) mobilization induced by melittin. Acteoside reduced the catecholamine release and raised the amount of intracellular chromogranin A which is co-released with catecholamine from melittin-stimulated PC12 cells. Taken together, our results suggest that acteoside could suppress the exocytosis via inhibition of Ca(2+)-dependent PLA2 and extracellular Ca(2+) influx in PC12 cells stimulated by melittin.

To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca2+ mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca2+ mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca2+, stearic acid (100 µM) did not cause any increase of intracellular Ca2+ mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca2+ mobilization, but the increase was smaller than that in the presence of extracellular Ca2+. These results suggest that C18 fatty acid-induced intracellular Ca2+ mobilization is mainly dependent on extracellular Ca2+ influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca2+ mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca2+ mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca2+ mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca2+ mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation.