Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation

1987 ◽  
Vol 252 (4) ◽  
pp. H721-H732 ◽  
Author(s):  
T. M. Burke ◽  
M. S. Wolin
Keyword(s):  
Hydrogen Peroxide ◽  
Guanylate Cyclase ◽  
Superoxide Anion ◽  
Vascular Tone ◽  
Soluble Guanylate Cyclase ◽  
Compound I ◽  
Cyclase Activation ◽  
Arterial Relaxation ◽  
Pulmonary Arterial ◽  
Guanylate Cyclase Activation

Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 microM were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 microM). Micromolar concentrations of hydrogen peroxide elicit time- and concentration-dependent increase in arterial levels of guanosine 3',5'-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension.

scholarly journals Molecular steps in soluble guanylate cyclase activation

2005 ◽  
Vol 5 (Suppl 1) ◽  
pp. S1
Author(s):  
Elizabeth M Boon ◽  
Stephen PL Cary ◽  
Shirley H Huang ◽  
Jonathan A Winger ◽  
Michael A Marletta
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

Superoxide anion inhibits cGMP-associated bovine pulmonary arterial relaxation

1990 ◽  
Vol 259 (4) ◽  
pp. H1056-H1062 ◽  
Author(s):  
P. D. Cherry ◽  
H. A. Omar ◽  
K. A. Farrell ◽  
J. S. Stuart ◽  
M. S. Wolin
Keyword(s):  
Guanylate Cyclase ◽  
Superoxide Anion ◽  
Pulmonary Arteries ◽  
Electron Donors ◽  
O2 Consumption ◽  
Cyclic Monophosphate ◽  
Arterial Relaxation ◽  
Diethyldithiocarbamic Acid ◽  
Pulmonary Arterial ◽  
Ly 83583

We have reported evidence that endothelium-independent relaxations of isolated bovine pulmonary arteries to H2O2 and to reoxygenation with 95% O2-5% CO2 after brief exposure to N2 (5% CO2) appear to be mediated by the activation of guanylate cyclase via H2O2 metabolism through catalase. Treatment of endothelium-removed pulmonary arteries with a potential guanylate cyclase-inhibitor, LY 83583, or with the inhibitor of the Zn+2, Cu+2-superoxide dismutase (SOD) diethyldithiocarbamic acid (DETCA), antagonized guanosine 3',5'-cyclic monophosphate (cGMP)-associated relaxation to H2O2, to reoxygenation and to glyceryl trinitrate, but not the adenosine 3',5'-cyclic monophosphate-associated relaxation to isoproterenol. Superoxide anion (O2-.) levels, detected by lucigenin-elicited chemiluminescence, were enhanced by LY 83583 or DETCA treatment of pulmonary arteries at ambient PO2. Chemiluminescence produced by LY 83583 was markedly potentiated by DETCA treatment, decreased at addition of exogenous SOD, and inhibited markedly by anoxia. LY 83583, but not DETCA, stimulated cyanide-insensitive O2 consumption, consistent with redox cycling of the compound independent of mitochondrial respiration. We propose that O2-. generated on the metabolism of LY 83583, or from cellular electron donors after SOD inhibition by DETCA, inhibits cGMP-mediated relaxations of pulmonary arteries.

Effects of soluble guanylate cyclase activation on heart transplantation in a rat model

2015 ◽  
Vol 34 (10) ◽  
pp. 1346-1353 ◽  
Author(s):  
Sivakkanan Loganathan ◽  
Sevil Korkmaz-Icöz ◽  
Tamás Radovits ◽  
Shiliang Li ◽  
Beatrice Mikles ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Guanylate Cyclase ◽  
Rat Model ◽  
Soluble Guanylate Cyclase ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

Identification of residues crucially involved in soluble guanylate cyclase activation

FEBS Letters ◽  
2006 ◽  
Vol 580 (17) ◽  
pp. 4205-4213 ◽  
Author(s):  
Christiane Rothkegel ◽  
Peter M. Schmidt ◽  
Friederike Stoll ◽  
Henning Schröder ◽  
Harald H.H.W. Schmidt ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

scholarly journals Probing Soluble Guanylate Cyclase Activation by CO and YC-1 Using Resonance Raman Spectroscopy

Biochemistry ◽  
2010 ◽  
Vol 49 (18) ◽  
pp. 3815-3823 ◽  
Author(s):  
Mohammed Ibrahim ◽  
Emily R. Derbyshire ◽  
Michael A. Marletta ◽  
Thomas G. Spiro
Keyword(s):  
Raman Spectroscopy ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Resonance Raman Spectroscopy ◽  
Resonance Raman ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

scholarly journals Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn

2005 ◽  
Vol 289 (4) ◽  
pp. L660-L666 ◽  
Author(s):  
Stephen Wedgwood ◽  
Robin H. Steinhorn ◽  
Melisa Bunderson ◽  
Jason Wilham ◽  
Satyan Lakshminrusimha ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Persistent Pulmonary Hypertension ◽  
Ovine Model ◽  
Ros Scavenger ◽  
Pulmonary Arterial ◽  
Initial Objective

Similar to infants born with persistent pulmonary hypertension of the newborn (PPHN), there is an increase in circulating endothelin-1 (ET-1) and decreased cGMP-mediated vasodilation in an ovine model of PPHN. These abnormalities lead to vasoconstriction and vascular remodeling. Our previous studies have demonstrated that reactive oxygen species (ROS) levels are increased in pulmonary arterial smooth muscle cells (PASMC) exposed to ET-1. Thus the initial objective of this study was to determine whether the development of pulmonary hypertension in utero is associated with elevated production of the ROS hydrogen peroxide (H2O2) and if this is associated with alterations in antioxidant capacity. Second we wished to determine whether chronic exposure of PASMC isolated from fetal lambs to H2O2 would mimic the decrease in soluble guanylate cyclase expression observed in the ovine model of PPHN. Our results indicate that H2O2 levels are significantly elevated in pulmonary arteries isolated from 136-day-old fetal PPHN lambs ( P 0.05). In addition, we determined that catalase and glutathione peroxidase expression and activities remain unchanged. Also, we found that the overnight exposure of fetal PASMC to a H2O2-generating system resulted in significant decreases in soluble guanylate cyclase expression and nitric oxide (NO)-dependent cGMP generation ( P 0.05). Finally, we demonstrated that the addition of the ROS scavenger catalase to isolated pulmonary arteries normalized the vasodilator responses to exogenous NO. As these scavengers had no effect on the vasodilator responses in pulmonary arteries isolated from age-matched control lambs this enhancement appears to be unique to PPHN. Overall our data suggest a role for H2O2 in the abnormal vasodilation associated with the pulmonary arteries of PPHN lambs.

scholarly journals Direct soluble guanylate cyclase activation improves vascular function in a mouse model of sickle cell disease

Nitric Oxide ◽  
2014 ◽  
Vol 42 ◽  
pp. 138
Author(s):  
Karin Potoka ◽  
Christina Mucci ◽  
Stephanie Mutchler ◽  
Marta Bueno ◽  
Eva Becker-Pelster ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mouse Model ◽  
Sickle Cell ◽  
Guanylate Cyclase ◽  
Vascular Function ◽  
Soluble Guanylate Cyclase ◽  
Cell Disease ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation
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