ABSTRACT
The mechanism is unclear for the reported protective effect of hyperbaric oxygen preconditioning against oxidative stress in tissues, and the distinct effects of hyperbaric oxygen applied after stress. The trained mice were divided into three groups: the control, hyperbaric oxygenation preconditioning, and hyperbaric oxygenation applied after mild (fasting) or hard (prolonged exercise) stress. After preconditioning, we observed a decrease in basal levels of nitric oxide, tetrahydrobiopterin, and catalase despite the drastic increase in inducible and endothelial nitric oxide synthases. Moreover, the basal levels of glutathione, related enzymes, and nitrosative stress only increased in the preconditioning group. The control and preconditioning groups showed a similar mild stress response of the endothelial and neuronal nitric oxide synthases. At the same time, the activity of all nitric oxide synthase, glutathione (GSH) in muscle, declined in the experimental groups but increased in control during hard stress. The results suggested that hyperbaric oxygen preconditioning provoked uncoupling of nitric oxide synthases and the elevated levels of GSH in muscle during this study, while hyperbaric oxygen applied after stress showed a lower level of GSH but higher recovery post-exercise levels in the majority of antioxidant enzymes. We discuss the possible mechanisms of the redox response and the role of the nitric oxide in this process.
ABSTRACT
The relaxant effect of the lactone of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g) with and without endothelium, precontracted with 1.0 microM phenylephrine. The lactone presented a greater potency than rosuvastatin in relaxing aortic rings. Unlike rosuvastatin, the effect of its lactone was endothelium-independent. Pretreatment with either indomethacin (10 microM) or mevalonate (1 mM) did not inhibit the relaxant effect of the lactone. L-NAME (10 microM), 1400 W (10 microM), or tetraethylammonium (TEA, 10 mM) partially inhibited the relaxant effect of the lactone on endothelium-denuded aortic rings. However, cycloheximide (10 microM) or the combination of TEA plus L-NAME completely inhibited the relaxant effect. The NOS-2 was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with lactone treated rings. In conclusion, rosuvastatin was associated with a relaxant effect dependent on both endothelium and HMG-CoA reductase in rat aorta, whereas the lactone exhibited an endothelium and HMG-CoA reductase-independent relaxant effect. Both nitric oxide produced by NOS-2 and K+ channels are involved in the relaxant effect of the lactone.
