scholarly journals Reactive Oxygen Species Scavengers Improve Voltage-Gated K+Channel Function in Pulmonary Arteries of Newborn Pigs with Progressive Hypoxia-Induced Pulmonary Hypertension

2013 ◽  
Vol 3 (3) ◽  
pp. 551-563 ◽  
Author(s):  
Candice D. Fike ◽  
Judy L. Aschner ◽  
Mark R. Kaplowitz ◽  
Yongmei Zhang ◽  
Jane A. Madden
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Pulmonary Arteries ◽  
Reactive Oxygen ◽  
K Channel ◽  
Oxygen Species ◽  
Voltage Gated ◽  
Channel Function ◽  
Progressive Hypoxia ◽  
Newborn Pigs

scholarly journals PKCβ and reactive oxygen species mediate enhanced pulmonary vasoconstrictor reactivity following chronic hypoxia in neonatal rats

2020 ◽  
Vol 318 (2) ◽  
pp. H470-H483 ◽  
Author(s):  
Joshua R. Sheak ◽  
Simin Yan ◽  
Laura Weise-Cross ◽  
Rosstin Ahmadian ◽  
Benjimen R. Walker ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Chronic Hypoxia ◽  
Primary Cultures ◽  
Pulmonary Arteries ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neonatal Rats ◽  
Basal Tone

Reactive oxygen species (ROS), mitochondrial dysfunction, and excessive vasoconstriction are important contributors to chronic hypoxia (CH)-induced neonatal pulmonary hypertension. On the basis of evidence that PKCβ and mitochondrial oxidative stress are involved in several cardiovascular and metabolic disorders, we hypothesized that PKCβ and mitochondrial ROS (mitoROS) signaling contribute to enhanced pulmonary vasoconstriction in neonatal rats exposed to CH. To test this hypothesis, we examined effects of the PKCβ inhibitor LY-333,531, the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL), and the mitochondrial antioxidants mitoquinone mesylate (MitoQ) and (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) on vasoconstrictor responses in saline -perfused lungs (in situ) or pressurized pulmonary arteries from 2-wk-old control and CH (12-day exposure, 0.5 atm) rats. Lungs from CH rats exhibited greater basal tone and vasoconstrictor sensitivity to 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619). LY-333,531 and TEMPOL attenuated these effects of CH, while having no effect in lungs from control animals. Basal tone was similarly elevated in isolated pulmonary arteries from neonatal CH rats compared with control rats, which was inhibited by both LY-333,531 and mitochondria-targeted antioxidants. Additional experiments assessing mitoROS generation with the mitochondria-targeted ROS indicator MitoSOX revealed that a PKCβ-mitochondrial oxidant signaling pathway can be pharmacologically stimulated by the PKC activator phorbol 12-myristate 13-acetate in primary cultures of pulmonary artery smooth muscle cells (PASMCs) from control neonates. Finally, we found that neonatal CH increased mitochondrially localized PKCβ in pulmonary arteries as assessed by Western blotting of subcellular fractions. We conclude that PKCβ activation leads to mitoROS production in PASMCs from neonatal rats. Furthermore, this signaling axis may account for enhanced pulmonary vasoconstrictor sensitivity following CH exposure. NEW & NOTEWORTHY This research demonstrates a novel contribution of PKCβ and mitochondrial reactive oxygen species signaling to increased pulmonary vasoconstrictor reactivity in chronically hypoxic neonates. The results provide a potential mechanism by which chronic hypoxia increases both basal and agonist-induced pulmonary arterial smooth muscle tone, which may contribute to neonatal pulmonary hypertension.

Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing

2004 ◽  
Vol 11 (2) ◽  
pp. 171-178 ◽  
Author(s):  
Xiang Dong Tang ◽  
Maria L Garcia ◽  
Stefan H Heinemann ◽  
Toshinori Hoshi
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Bk Channel ◽  
Oxygen Species ◽  
Channel Function ◽  
Calcium Sensing

scholarly journals Arachidonic acid- and prostaglandin E2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets

2011 ◽  
Vol 301 (6) ◽  
pp. H2482-H2487 ◽  
Author(s):  
Alie Kanu ◽  
Charles W. Leffler
Keyword(s):  
Reactive Oxygen Species ◽  
Carbon Monoxide ◽  
Arachidonic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Artificial Cerebrospinal Fluid ◽  
Newborn Pigs ◽  
Cerebral Vasodilation ◽  
Prostacyclin Analog ◽  
Cerebral Vascular

Arachidonic acid (AA) and prostaglandin (PG) E2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10−8-10−6 M), PGE2 (10−8-10−6 M), iloprost (10−8-10−6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 × 10−5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 × 10−5 M) and the H2O2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE2. Heme-l-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE2-induced cerebral vascular dilation is mediated by CO, independent of ROS.

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