Endothelium-derived reactive oxygen species: their relationship to endothelium-dependent hyperpolarization and vascular tone

Abstract

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.

Identification of 15-hydroxy-11,12-epoxyeicosatrienoic acid as a vasoactive 15-lipoxygenase metabolite in rabbit aorta

“…CDU (10 Ϫ6 M) did not change the pattern of [ 14 C]AA metabolism to a great extent (data not shown). The proximity of the olefin to the epoxy group activates the epoxide of 15-H-11,12-EETA to hydrolysis in acid to 11,12,14,. For example, at pH 3.0, 15-H-11,12-EETA has a half-life of ϳ50 s. For efficient extraction of the HEETAs and THETAs, the samples must be acidified to pH 3.5.…”

“…We have proposed that AA is metabolized sequentially by 15-LO-I and hydroperoxide isomerase to produce hydroxyepoxyeicosatrienoic acids (HEETAs), which are hydrolyzed by soluble epoxide hydrolase (sEH) to trihydroxyeicosatrienoic acids (THETAs) (40,42). The 15-LO-I metabolite 11(R),12(S),15(S)-trihydroxyeicosa-5(Z),8(Z),13(E)-trienoic acid (11,12,15-THETA) was isolated and identified from rabbit aorta and mesenteric arteries and shown to function as an EDHF (6,18,19,40,52). 11,12,15-THETA hyperpolarizes and relaxes the SMCs of rabbit aorta through opening of apamin-sensitive K ϩ channels (19).…”

Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats

“…EDHF is another vasoactive substance and it has been found in rat, horse and human penile small arteries [5][6][7][8]17]. Moreover, in systemic arteries, several EDHF candidates have been suggested, including potassium ions, products of the cytochrome P450 pathway, C-type natriuretic peptide, hydrogen peroxide and K + [7,18,19]. EDHF-mediated relaxation is dependent on the activation of endothelial SK3 and IK1, which can be blocked by the combination of apamin and charybdotoxin.…”

Free Radical Scavenging Properties of Skin and Pulp Extracts of Different Grape Cultivars In Vitro and Attenuation of H2O2-Induced Oxidative Stress in Liver Tissue Ex Vivo

“…Reactive oxygen and nitrogen species (RONS), the byproducts of cellular metabolic activity, are a wide range of small signaling molecules that include free radicals such as superoxide anion radical, hydroxyl radical, peroxynitrite (ONOO-), and non-free-radicals such as hydrogen peroxide and singlet oxygen [1,2]. These are constantly generated in cells during normal oxidative processes through a variety of pathways, including both enzyme-catalyzed reactions and nonenzymatic reactions [3].…”