Neutral sphingomyelinase, NADPH oxidase and reactive oxygen species. Role in acute hypoxic pulmonary vasoconstriction

2011 ◽  
Vol 226 (10) ◽  
pp. 2633-2640 ◽  
Author(s):  
Giovanna Frazziano ◽  
Laura Moreno ◽  
Javier Moral-Sanz ◽  
Carmen Menendez ◽  
Lucía Escolano ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neutral Sphingomyelinase ◽  
Pulmonary Vasoconstriction

scholarly journals Recent advances in oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

2017 ◽  
Vol 123 (6) ◽  
pp. 1647-1656 ◽  
Author(s):  
Ievgen Strielkov ◽  
Oleg Pak ◽  
Natasha Sommer ◽  
Norbert Weissmann
Keyword(s):  
Reactive Oxygen Species ◽  
Transient Receptor Potential ◽  
Oxygen Sensing ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Complex Iii ◽  
Oxygen Species ◽  
Pulmonary Vasoconstriction ◽  
Transient Receptor

Hypoxic pulmonary vasoconstriction (HPV) is a physiological reaction, which adapts lung perfusion to regional ventilation and optimizes gas exchange. Impaired HPV may cause systemic hypoxemia, while generalized HPV contributes to the development of pulmonary hypertension. The triggering mechanisms underlying HPV are still not fully elucidated. Several hypotheses are currently under debate, including a possible decrease as well as an increase in reactive oxygen species as a triggering event. Recent findings suggest an increase in the production of reactive oxygen species in pulmonary artery smooth muscle cells by complex III of the mitochondrial electron transport chain and occurrence of oxygen sensing at complex IV. Other essential components are voltage-dependent potassium and possibly L-type, transient receptor potential channel 6, and transient receptor potential vanilloid 4 channels. The release of arachidonic acid metabolites appears also to be involved in HPV regulation. Further investigation of the HPV mechanisms will facilitate the development of novel therapeutic strategies for the treatment of HPV-related disorders.

Reactive Oxygen Species Scavengers Attenuate Endotoxin-induced Impairment of Hypoxic Pulmonary Vasoconstriction in Mice

2002 ◽  
Vol 97 (5) ◽  
pp. 1227-1233 ◽  
Author(s):  
Hemanth A. Baboolal ◽  
Fumito Ichinose ◽  
Roman Ullrich ◽  
Noriko Kawai ◽  
Kenneth D. Bloch ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Injury ◽  
Saline Solution ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intratracheal Administration ◽  
Endotoxin Challenge ◽  
Pulmonary Vasoconstriction ◽  
Ros Scavengers

Background Sepsis and endotoxemia attenuate hypoxic pulmonary vasoconstriction (HPV), thereby impairing systemic oxygenation. Reactive oxygen species (ROS) are implicated in the pathogenesis of sepsis-induced lung injury. The authors investigated whether treatment with scavengers of ROS prevents impairment of HPV in mice challenged with endotoxin. Methods The pulmonary vasoconstrictor response to left mainstem bronchus occlusion (LMBO) was studied in anesthetized mice 22 h after an intraperitoneal challenge with saline solution or 10 mg/kg Escherichia coli endotoxin. In some mice, challenge with saline solution or endotoxin was followed after 1 h with intraperitoneal or intratracheal administration of the ROS scavengers N-acetylcysteine or EUK-8. Myeloperoxidase activity and nitric oxide synthase-2 gene expression were measured in lung tissues. Results The LMBO increased left pulmonary vascular resistance by 106 +/- 24% in saline-challenged control mice but by only 23 +/- 12% (P < 0.05) in endotoxin-challenged mice. Intraperitoneal administration of N-acetylcysteine or EUK-8 1 h after endotoxin challenge attenuated the endotoxin-induced impairment of HPV (58 +/- 6% and 68 +/- 10%, respectively; both P< 0.05 endotoxin-challenged mice). Intratracheal administration of ROS scavengers 1 h after endotoxin challenge was equally effective but required lower doses than systemic treatment. Administration of the ROS scavengers 22 h after endotoxin challenge did not restore HPV. Conclusions Administration of N-acetylcysteine or EUK-8 1 h after endotoxin challenge in mice prevented the impairment of HPV after LMBO. Early therapy with ROS scavengers, either systemically or by inhalation, may provide a means to preserve HPV in sepsis-associated acute lung injury.

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