Active oxygen species as signaling mediators in the vascular system

RESUMO

There is increasing evidence that active oxygen species (AOS) can act as autocrine or paracrine regulatory mediators, perhaps as part of a more general cellular redox messenger system. This signaling role of AOS has been particularly studied in the vascular system, considering that 1) Nitric oxide, a gaseous free radical, or a related compound, is a major endothelium-derived vasodilator which is scavenged by superoxide. This interaction not only promotes vasoconstriction, but can generate peroxynitrite, which may be toxic to cells; 2) AOS modulate cytoplasmic calcium and hydrogen concentration and are related to other messenger systems such as membrane G-proteins and protein kinase C; 3) through EPR techniques we showed recently that in vitro and in vivo release of vascular free radicals (probably superoxide) can be triggered by physiological stimuli such as shear stress increases. Flow-induced spin adduct signals were abolished by endothelium removal; 4) we showed previously that superoxide dismutase completely prevents vasoconstriction soon after vascular injury induced by angioplasty, thus implicating the superoxide radical in this acute phenomenon. In addition, we showed that allopurinol or N-acetylcysteine markedly increases vascular diameter up to 7 days after vascular injury, suggesting that redox phenomena may be involved in sustained vessel recoil; 5) endothelial free radical production is increased in atherosclerosis; likewise, lipoprotein oxidation within the vascular wall appears to be a critical in vivo step for atherogenesis. In addition, oxidative stress contributes to dysfunction of endothelium-dependent relaxation in hypertension and diabetes; 6) AOS were shown to mediate growth-related responses in vascular cells. Recently, we showed that in vivo administration of oxidized glutathione markedly enhances vascular proliferation after injury. Therefore , it is suggested that AOS may work as vascular mediators that may exert useful physiological roles; derangements of redox signaling mechanisms are likely involved in endothelial dysfunction and pathological vascular responses.