Nitrate tolerance does not increase production of peroxynitrite in the heart

2002 ◽  
Vol 283 (1) ◽  
pp. H69-H76 ◽  
Author(s):  
Tamás Csont ◽  
Csaba Csonka ◽  
Annamária Ónody ◽  
Anikó Görbe ◽  
László Dux ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Nitrate Tolerance ◽  
Oxygen Species ◽  
Mechanical Function ◽  
Nitrate Treatment

Clinical studies have suggested that long-term nitrate treatment does not improve and may even worsen cardiovascular mortality, and the possible role of nitrate tolerance has been suspected. Nitrate tolerance has been recently shown to increase vascular superoxide and peroxynitrite production leading to vascular dysfunction. Nevertheless, nitrates exert direct cardiac effects independent from their vascular actions. Therefore, we investigated whether in vivo nitroglycerin treatment leading to vascular nitrate tolerance increases cardiac formation of nitric oxide (NO), reactive oxygen species, and peroxynitrite, thereby leading to cardiac dysfunction. Nitrate tolerance increased bioavailability of NO in the heart without increasing formation of reactive oxygen species. Despite elevated myocardial NO, neither cardiac markers of peroxynitrite formation nor cardiac mechanical function were affected by nitroglycerin treatment. However, serum free nitrotyrosine, a marker for systemic peroxynitrite formation, was significantly elevated in nitroglycerin-treated animals. This is the first demonstration that, although the systemic effects of nitroglycerin may be deleterious due to enhancement of extracardiac peroxynitrite formation, nitroglycerin does not result in oxidative damage in the heart.

Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors

2008 ◽  
Vol 294 (4) ◽  
pp. F719-F728 ◽  
Author(s):  
Armin Just ◽  
Christina L. Whitten ◽  
William J. Arendshorst
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Long Term Effects ◽  
Vasomotor Tone ◽  
Chronic Stimulation ◽  
Renal Vasoconstriction ◽  
Oxidase Inhibition

Reactive oxygen species (ROS) play important roles in renal vasoconstrictor responses to acute and chronic stimulation by angiotensin II and norepinephrine, as well as in long-term effects of endothelin-1 (ET-1). Little is known about participation of ROS in acute vasoconstriction produced by ET-1. We tested the influence of NAD(P)H oxidase inhibition by apocynin [4 mg·kg−1·min−1, infused into the renal artery (ira)] on ETA and ETB receptor signaling in the renal microcirculation. Both receptors were stimulated by ET-1, ETA receptors by ET-1 during ETB antagonist BQ-788, and ETB by ETB agonist sarafotoxin 6C. ET-1 (1.5 pmol injected ira) reduced renal blood flow (RBF) 17 ± 4%. Apocynin raised baseline RBF (+10 ± 1%, P < 0.001) and attenuated the ET-1 response to 10 ± 2%, i.e., 35 ± 9% inhibition ( P < 0.05). Apocynin reduced ETA-induced vasoconstriction by 42 ± 12% ( P < 0.05) and that of ETB stimulation by 50 ± 8% ( P < 0.001). During nitric oxide (NO) synthase inhibition ( Nω-nitro-l-arginine methyl ester), apocynin blunted ETA-mediated vasoconstriction by 60 ± 8% ( P < 0.01), whereas its effect on the ETB response (by 87 ± 8%, P < 0.001) was even larger without than with NO present ( P < 0.05). The cell-permeable superoxide dismutase mimetic tempol (5 mg·kg−1·min−1 ira), which reduces O2− and may elevate H2O2, attenuated ET-1 responses similar to apocynin (by 38 ± 6%, P < 0.01). We conclude that ROS, O2− rather than H2O2, contribute substantially to acute renal vasoconstriction elicited by both ETA and ETB receptors and to basal renal vasomotor tone in vivo. This physiological constrictor action of ROS does not depend on scavenging of NO. In contrast, scavenging of O2− by NO seems to be more important during ETB stimulation.

The Role of Reactive Oxygen Species in the Light-Induced Deformation of DNA

1984 ◽  
Vol 39 (9) ◽  
pp. 1276-1280 ◽  
Author(s):  
R. Baumann ◽  
M. Herrmann ◽  
H. Parlar
Keyword(s):  
Reactive Oxygen Species ◽  
Excited States ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
In Vivo Experiments ◽  
Pyrimidine Bases ◽  
Effect Of Oxygen

Dimerizations and reactions with water of pyrimidine bases are the primary steps held respon­sible for the deformation of DNA at short wavelengths in vitro and in vivo experiments. However the influence of oxygen in combination with water on the UV deformation at wavelengths rep­resentative for troposphere is evident from the observed data and both together are needed to change the DNA structure. The only plausible explanation for the effect of oxygen is the forma­tion of reactive oxygen species during the UV irradiation of DNA. In the present work the deformation of DNA by different oxygen species like singlet oxygen (1O2), superoxideanion (O2-), hydroxyradical (·OH), ozone (O3) and hydrogenperoxide (H2O2) is excluded with the help of chemical-trapping experiments. The photo-induced transformation proceeds via excited states of DNA. which react with groundstate oxygen to afford peroxide.

scholarly journals AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4030-4038 ◽  
Author(s):  
Marisa M. Juntilla ◽  
Vineet D. Patil ◽  
Marco Calamito ◽  
Rohan P. Joshi ◽  
Morris J. Birnbaum ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Function ◽  
Reactive Oxygen ◽  
Lymphoid Cells ◽  
Oxygen Species ◽  
Cellular Functions ◽  
Hematopoietic Stem ◽  
G0 Phase

Although AKT is essential for multiple cellular functions, the role of this kinase family in hematopoietic stem cells (HSCs) is unknown. Thus, we analyzed HSC function in mice deficient in the 2 isoforms most highly expressed in the hematopoietic compartment, AKT1 and AKT2. Although loss of either isoform had only a minimal effect on HSC function, AKT1/2 double-deficient HSCs competed poorly against wild-type cells in the development of myeloid and lymphoid cells in in vivo reconstitution assays. Serial transplantations revealed an essential role for AKT1 and AKT2 in the maintenance of long-term HSCs (LT-HSCs). AKT1/2 double-deficient LT-HSCs were found to persist in the G0 phase of the cell cycle, suggesting that the long-term functional defects are caused by increased quiescence. Furthermore, we found that the intracellular content of reactive oxygen species (ROS) is dependent on AKT because double-deficient HSCs demonstrate decreased ROS. The importance of maintaining ROS for HSC differentiation was shown by a rescue of the differentiation defect after pharmacologically increasing ROS levels in double-deficient HSCs. These data implicate AKT1 and AKT2 as critical regulators of LT-HSC function and suggest that defective ROS homeostasis may contribute to failed hematopoiesis.

scholarly journals Attenuation of Ischemia-Induced Mouse Brain Injury by SAG, a Redox-Inducible Antioxidant Protein

2001 ◽  
Vol 21 (6) ◽  
pp. 722-733 ◽  
Author(s):  
Guo-Yuan Yang ◽  
Li Pang ◽  
Hai-Liang Ge ◽  
Mingjia Tan ◽  
Wen Ye ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Brain Injury ◽  
Mouse Brain ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Model Systems ◽  
Oxygen Species ◽  
Antioxidant Protein

Cerebral ischemia resulting from a disruption of blood flow to the brain initiates a cascade of events that causes neuron death and leads to neurologic dysfunction. Reactive oxygen species are thought, at least in part, to mediate this disease process. The authors recently cloned and characterized an antioxidant protein, SAG (sensitive to apoptosis gene), that is redox inducible and protects cells from apoptosis induced by redox agents in a number of in vitro cell model systems. This study reports a neuroprotective role of SAG in ischemia/reperfusion-induced brain injury in an in vivo mouse model. SAG was expressed at a low level in brain tissue and was inducible after middle cerebral artery occlusion with peak expression at 6 to 12 hours. At the cellular level, SAG was mainly expressed in the cytoplasm of neurons and astrocytes, revealed by double immunofluorescence. An injection of recombinant adenoviral vector carrying human SAG into mouse brain produced an overexpression of SAG protein in the injected areas. Transduction of AdCMVSAG (wild-type), but not AdCMVmSAG (mutant), nor the AdCMVlacZ control, protected brain cells from ischemic brain injury, as evidenced by significant reduction of the infarct areas where SAG was highly expressed. The result suggests a rather specific protective role of SAG in the current in vivo model. Mechanistically, SAG overexpression decreased reactive oxygen species production and reduced the number of apoptotic cells in the ischemic areas. Thus, antioxidant SAG appears to protect against reactive oxygen species–induced brain damage in mice. Identification of SAG as a neuroprotective molecule could lead to potential stroke therapies.

Vascular Dysfunction of Venous Bypass Conduits Is Mediated by Reactive Oxygen Species in Diabetes: Role of Endothelin-1

2004 ◽  
Vol 313 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Adviye Ergul ◽  
Jeanette Schultz Johansen ◽  
Catherine Strømhaug ◽  
Alex K. Harris ◽  
Jimmie Hutchinson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Venous Bypass ◽  
Endothelin 1
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