scholarly journals Endogenous Endothelin‐1 Contributes to Enhanced Basal Pulmonary Arterial Tone Following Chronic Hypoxia: Role of Mitochondria‐Derived Reactive Oxygen Species

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Simin Yan ◽  
Nikki Jernigan ◽  
Thomas Resta
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Endothelin 1 ◽  
Pulmonary Arterial ◽  
Arterial Tone

scholarly journals Reactive Oxygen Species Production in the Early and Later Stage of Chronic Ventilatory Hypoxia

2012 ◽  
pp. 145-151 ◽  
Author(s):  
D. HODYC ◽  
E. JOHNSON ◽  
A. SKOUMALOVÁ ◽  
J. TKACZYK ◽  
H. MAXOVÁ ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
No Production ◽  
Oxygen Species ◽  
Air Plasma ◽  
Species Production ◽  
Specific Timing

Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension.

scholarly journals Membrane depolarization is required for pressure-dependent pulmonary arterial tone but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402097355
Author(s):  
Charles E Norton ◽  
Nikki L Jernigan ◽  
Benjimen R Walker ◽  
Thomas C Resta
Keyword(s):  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Rho Kinase ◽  
Membrane Depolarization ◽  
Src Kinases ◽  
Endothelin 1 ◽  
Receptor Inhibition ◽  
Pulmonary Arterial ◽  
Arterial Tone

Enhanced vasoconstriction is increasingly identified as an important contributor to the development of pulmonary hypertension. Chronic hypoxia results in enhanced Rho kinase mediated Ca2+ sensitization contributing to pressure-dependent pulmonary arterial tone as well as augmented vasoconstriction to endothelin-1 and depolarizing stimuli. We sought to investigate the interaction between these vasoconstrictor stimuli in isolated, pressurized, pulmonary arteries. We used the K+ ionophore, valinomycin, to clamp membrane potential (Vm) to investigate the role of membrane depolarization in endothelin-1 and pressure-dependent constriction, and endothelin-1 receptor inhibitors to determine whether membrane depolarization or stretch signal through endothelin-1 receptors. Clamping Vm prevented pressure-dependent tone, but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia. Furthermore, endothelin-1 receptor inhibition had no effect on either pressure-dependent tone or vasoconstriction to KCl. As Src kinases contribute to both pressure-dependent tone and enhanced endothelin-1 vasoconstriction following chronic hypoxia, we further investigated their role in depolarization-induced vasoconstriction. Inhibition of Src kinases attenuated enhanced vasoconstriction to KCl. We conclude that membrane depolarization contributes to pressure-dependent tone but not enhanced vasoconstriction to ET-1, and that Src kinases serve as upstream mediators facilitating enhanced Rho kinase-dependent vasoconstriction following chronic hypoxia.

scholarly journals Pulmonary Arterial Responses to Reactive Oxygen Species Are Altered in Newborn Piglets With Chronic Hypoxia-Induced Pulmonary Hypertension

2011 ◽  
Vol 70 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Candice D Fike ◽  
Judy L Aschner ◽  
James C Slaughter ◽  
Mark R Kaplowitz ◽  
Yongmei Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Newborn Piglets ◽  
Pulmonary Arterial ◽  
Arterial Responses

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

Endothelium-derived reactive oxygen species and endothelin-1 attenuate NO-dependent pulmonary vasodilation following chronic hypoxia

2004 ◽  
Vol 287 (4) ◽  
pp. L801-L808 ◽  
Author(s):  
Nikki L. Jernigan ◽  
Benjimen R. Walker ◽  
Thomas C. Resta
Keyword(s):  
Reactive Oxygen Species ◽  
Receptor Antagonist ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Inhibitory Influence ◽  
Oxygen Species ◽  
No Donor ◽  
Endothelin 1 ◽  
Pulmonary Vasodilation ◽  
Spermine Nonoate

Vasodilatory responses to exogenous nitric oxide (NO) are diminished following exposure to chronic hypoxia (CH) in isolated, perfused rat lungs. We hypothesized that both endothelium-derived reactive oxygen species (ROS) and endothelin-1 (ET-1) mediate this attenuated NO-dependent pulmonary vasodilation following CH. To test this hypothesis, we examined vasodilatory and vascular smooth muscle (VSM) Ca2+ responses to the NO donor spermine NONOate in UTP-constricted, isolated pressurized small pulmonary arteries from control and CH rats. Consistent with our previous findings in perfused lungs, we observed attenuated NO-dependent vasodilation following CH in endothelium-intact vessels. However, in endothelium-denuded vessels, responses to spermine NONOate were augmented in CH rats compared with controls, thus demonstrating an inhibitory influence of the endothelium on NO-dependent reactivity following CH. Whereas both the ROS scavenger tiron and the ETA receptor antagonist BQ-123 augmented NO-dependent reactivity in endothelium-intact vessels from CH rats, neither fully restored vasodilatory responses to those observed following endothelium denudation in vessels from CH rats. In contrast, the combination of tiron and BQ-123 or the nonselective ET receptor antagonist PD-145065 enhanced NO responsiveness in endothelium-intact vessels from CH rats similar to that observed following endothelium denudation. We conclude that both endothelium-derived ROS and ET-1 attenuate NO-dependent pulmonary vasodilation following CH. Furthermore, CH augments pulmonary VSM reactivity to NO.

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