Pleiotropic Effects of Hydrogen Peroxide in Arteries and Veins From Normotensive and Hypertensive Rats

Thakali, Keshari; Davenport, Lauren; Fink, Gregory D.; Watts, Stephanie W.

doi:10.1161/01.hyp.0000201540.91234.8f

Cited by 41 publications

(33 citation statements)

References 28 publications

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“…In support of this, contraction of rat aorta by hydrogen peroxide was attenuated by the removal of extracellular Ca 2ϩ . 31) However, the L-type Ca 2ϩ channel antagonist, nicardipine, did not inhibit sustained contraction induced by the purine and XOD system, indicating that ROS stimulates other type(s) of Ca 2ϩ channel directly and/or activates signaling cascades which affect Ca 2ϩ influx indirectly.…”

Section: Fig 5 Inhibitory Effects Of Various Ros Scavengers On Dysfmentioning

confidence: 92%

Sustained Contraction and Endothelial Dysfunction Induced by Reactive Oxygen Species in Porcine Coronary Artery

Ishihara

Sekine

Hatano

et al. 2008

Biological & Pharmaceutical Bulletin

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Reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide and hydroxyl radicals, can be produced in vivo by mechanisms related to mitochondrial respiration, xanthine oxidase (XOD), nitric oxide synthase (NOS), NADPH oxidase, and arachidonic acid metabolism.1,2) Disruption to one or more of these mechanisms is thought to be responsible for the pathogenesis of various diseases. [3][4][5][6] Of these mechanisms, XOD may be involved in the generation of ROS in the endothelium during ischemia and/or reperfusion. 7,8) Roy and McCord demonstrated that xanthine dehydrogenase is proteolytically converted to XOD in tissues within seconds or minutes of an ischemic episode, depending on the tissue involved. 9) Although both enzymes are involved in the catabolism of purine compounds, the latter transfers electrons to molecular oxygen to yield the ROS, superoxide anions and hydrogen peroxide. 10,11) Thus, the deleterious effects of reoxygenation or reperfusion in ischemic tissues can therefore be explained on the basis of the ROS produced by the xanthine-XOD (XϩXOD) system. For a better understanding of the pathogenesis of tissue damage by ROS, it is important to clarify which species of oxygen intermediates are involved in these events, and whether or not there are differences in sensitivity to ROS among various tissues.The direct effects of ROS on cultured vascular endothelial cells or isolated, perfused tissues have been extensively investigated, either by using ROS directly, or using a ROS-generating system, such as the XϩXOD system. [12][13][14][15][16][17] In these studies, ROS scavengers are used to clarify the species of ROS involved in these effects. Among the various biological effects attributed to ROS, vascular endothelial dysfunction has consistently been noted, irrespective of the preparations used. 2,18) In addition, ROS generated by the XϩXOD system caused contraction of rat pulmonary artery 19) and canine basilar artery, 20) whereas it relaxed canine coronary artery, 21) implying the existence of species or tissue differences in response to ROS. Furthermore, the responses of arteries to ROS are well-known to be influenced by the presence of endothelium. 12,13,16) Thus, the responses of the vasculature, including the endothelium, to ROS are complex, and the sensitivity to ROS probably varies depending on the tissue involved. Disruption to the functional integrity of blood vessels will inevitably alter the function of the organ supplied by these vessels. Thus, in the present study, we directed our attention to the effects of ROS on porcine coronary artery, in terms of muscular and endothelial functions, and attempted to determine characteristics of the responses of each vascular element, and to clarify the specific ROS involved. MATERIALS AND METHODS Preparation of Coronary Arterial RingsPorcine hearts, immersed in ice-cooled saline, were transported to the laboratory from an abattoir, usually within 1 h of death. The left anterior descending coronary artery was isolated 2-3 cm from its orig...

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Section: Fig 5 Inhibitory Effects Of Various Ros Scavengers On Dysfmentioning

confidence: 92%

Sustained Contraction and Endothelial Dysfunction Induced by Reactive Oxygen Species in Porcine Coronary Artery

Ishihara

Sekine

Hatano

et al. 2008

Biological & Pharmaceutical Bulletin

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“…It has been suggested that differences in the K + channel and/or Ca 2+ handling in various vascular beds or under different conditions may mediate these diverse actions of H2O2. In hypertensive rats, there is an increase in H2O2-induced contraction in arteries but not in veins, 18 and plasma H2O2 levels have been shown to correlate with mean arterial pressure in hypertensive patients. Overall, these findings suggest a role of ROS in vascular function and blood pressure regulation.…”

Section: (-S -) Thiyl Radical (-S · ) Disulfides (-S-s-) Disulfidementioning

confidence: 97%

Redox Regulation in the Extracellular Environment

Ottaviano

Handy

Loscalzo

2008

Circ J

128

100

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Molecular oxygen is involved in the oxidation of substrates used to produce energy; however, normal metabolism can also generate harmful (bio)chemical byproducts. These deleterious products are partially reduced forms of oxygen, and include free radicals such as superoxide anion radical, hydroxyl radical, or highly oxidizing non-radical species such as hydrogen peroxide (H2O2) and lipid peroxides, which are collectively known as ROS. 1 ROS typically derive from normal metabolism, activated leukocytes, and ambient oxygen in the environment. The production and accumulation of ROS and their downstream effects can be controlled or attenuated by antioxidants. When the ability of antioxidants to eliminate harmful cellular and extracellular ROS is compromised, the balance between ROS generation and antioxidant function to eliminate ROS is shifted in favor of an accumulation of oxidants, which defines the state of oxidative stress in a cell or organism. Oxidative damage can affect DNA, lipids, and proteins, and eventually compromise cell integrity. Many studies have implicated ROS in the pathological processes leading to heart disease, cancer, aging, AIDS, and inflammatory and autoimmune diseases.Oxidants, especially free radicals, are highly reactive. Superoxide can react within milliseconds with nitric oxide (NO) to produce peroxynitrite (ONOO -), a reactive nitrogen species (RNS). The nitrosium cation and nitroxyl anion are other RNS derived from NO. 2 Peroxynitrite is a strong oxidant involved in the nitrosative modification of proteins and lipids. Owing to its rapid reaction with NO, superoxide may modulate NO bioavailability and, subsequently, regulate vascular function. 3 Circulation Journal Vol.72, January 2008The cytosol, mitochondria, peroxisomes, and plasma are all potential sites of ROS formation. 4 The major sources of ROS are enzymatic via nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), xanthine oxidase, myeloperoxidase, endothelial NO synthase (eNOS), or as a consequence of normal mitochondrial respiration. In vascular cells, other enzymatic sources of ROS include cytochrome P450 isoenzymes, lipoxygenase, cyclooxygenase, heme oxygenase, and glucose oxidase. 1,3,[5][6][7] Most reviews to date have focused on the role of intracellular antioxidants that eliminate ROS from the intracellular environment. There are, however, several extracellular antioxidants that also play an equally important role in limiting ROS accumulation in the extracellular environment. Along with limiting ROS accumulation, extracellular redox status is essential for maintaining protein stability and function.The major enzymes important for the elimination of extracellular H2O2 are glutathione peroxidase-3 (GPx-3) and peroxiredoxin IV (Prx IV). Other extracellular antioxidants involved in ROS elimination include paraoxonase (PON), thioredoxin (Trx), Trx reductase (TrxR), glutaredoxin (Grx), extracellular superoxide dismutase (EC-SOD), and extracellular glutathione (GSH).Some of these antioxidants, notably glutathione...

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“…Several prohypertensive effects have been described for H2O2, such as increased vasoconstriction, vascular hypertrophy and hyperplasia, decreased diuresis and natriuresis and also increased spinal sympathetic outflow [7,50,[52][53][54][55][56][57][58]. Increasing evidence has also shown that H2O2 amplifies oxidative stress by stimulating ROS generation by NADPH oxidases, XO and eNOS [7,51].…”

Section: Rnsmentioning

confidence: 99%