Endothelium-derived reactive oxygen species: their relationship to endothelium-dependent hyperpolarization and vascular tone.
Opinions on the role of reactive oxygen species (ROS) in the vasculature have shifted in recent years, such that they are no longer merely regarded as indicators of cellular damage or byproducts of metabolism--they may also be putative mediators of physiological functions. Hydrogen peroxide (H2O2), in particular, can initiate vascular myocyte proliferation (and, incongruously, apoptosis), hyperplasia, cell adhesion, migration, and the regulation of smooth muscle tone. Endothelial cells express enzymes that produce ROS in response to various stimuli, and H2O2 is a potent relaxant of vascular smooth muscle. H2O2 itself can mediate endothelium-dependent relaxations in some vascular beds. Although nitric oxide (NO) is well recognized as an endothelium-derived dilator, it is also well established, particularly in the microvasculature, that another factor, endothelium-derived hyperpolarizing factor (EDHF), is a significant determinant of vasodilatory tone. This review primarily focuses on the hypothesis that H2O2 is an EDHF in resistance arteries. Putative endothelial sources of H2O2 and the effects of H2O2 on potassium channels, calcium homeostasis, and vascular smooth muscle tone are discussed. Furthermore, given the perception that ROS can more likely elicit cytotoxic effects than perform signalling functions, the arguments for and against H2O2 being an endogenous vasodilator are assessed.
Ellis
Anthie
A
Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, AB, Canada.
Triggle
Chris R
CR
D000818:Animals; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016232:Endothelins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide