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Exp Biol Med (Maywood). 2006 Mar;231(3):237-51.

Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction.

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Hypertension and Vascular Research Division, RM 7044, E&R Building, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202-2689, USA.


Numerous studies have demonstrated the ability of a variety of vascular cells, including endothelial cells, smooth muscle cells, and fibroblasts, to produce reactive oxygen species (ROS). Until recently, major emphasis was placed on the production of superoxide anion (O(2)(-)) in the vasculature as a result of its ability to directly attenuate the biological activity of endothelium-derived nitric oxide (NO). The short half-life and radius of diffusion of O(2)(-) drastically limit the role of this ROS as an important paracrine hormone in vascular biology. On the contrary, in recent years, the O(2)(-) metabolite hydrogen peroxide (H(2)O(2)) has increasingly been viewed as an important cellular signaling agent in its own right, capable of modulating both contractile and growth-promoting pathways with more far-reaching effects. In this review, we will assess the vascular production of H(2)O(2), its regulation by endogenous scavenger systems, and its ability to activate a variety of vascular signaling pathways, thereby leading to vascular contraction and growth. This discussion will include the ability of H(2)O(2) to (i) initiate calcium flux as well as (ii) stimulate pathways leading to sensitization of contractile elements to calcium. The latter involves a variety of protein kinases that have also been strongly implicated in vascular hypertrophy. Previous intensive study has emphasized the ability of NADPH oxidase-derived O(2)(-) and H(2)O(2) to activate these pathways in cultured smooth muscle cells. However, growing evidence indicates a considerably more complex array of unique oxidase systems in the endothelium, media, and adventitia that appear to participate in these deleterious effects in a sequential and temporal manner. Taken together, these findings seem consistent with a paracrine effect of H(2)O(2) across the vascular wall.

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