Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats

Belik, Jaques; Stevens, Danielle; Pan, Jingyi; McIntyre, Brendan A.S.; Kantores, Crystal; Ivanovska, Julijana; Xu, Emily; Ibrahim, Christine; Panama, Brian K.; Backx, Peter H.; McNamara, Patrick J.; Jankov, Robert P.

doi:10.1016/j.freeradbiomed.2010.07.021

Cited by 19 publications

(15 citation statements)

References 25 publications

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“…The functional evaluation of newborn pulmonary arteries has been previously described (1,18). Briefly, third-generation lung intralobar pulmonary artery ring segments (average diameter 80 -100 m and length ϭ 2 mm) were dissected free and mounted in a wire myograph (Danish Myo Technology).…”

Section: Organ Bath Studiesmentioning

confidence: 99%

“…A previously described newborn rat model of chronic hypoxiainduced pulmonary hypertension was used (1,7,14,18). Briefly, shortly after birth, newborn rats were continually exposed to 13% oxygen for 14 days in a computer-controlled environmental chamber (Oxycycler), as previously described (1).…”

Section: Chronic Hypoxia-induced Rat Model Of Neonatal Pulmonary Hypementioning

confidence: 99%

“…Briefly, shortly after birth, newborn rats were continually exposed to 13% oxygen for 14 days in a computer-controlled environmental chamber (Oxycycler), as previously described (1).…”

Section: Chronic Hypoxia-induced Rat Model Of Neonatal Pulmonary Hypementioning

confidence: 99%

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Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Enomoto

Jain

Pan

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Newborn rat response to single versus combined cGMP-dependent pulmonary vasodilators. Am J Physiol Lung Cell Mol Physiol 306: L207-L215, 2014. First published November 15, 2013 doi:10.1152/ajplung.00164.2013.-Inhaled nitric oxide (NO) and other cGMP-or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP-and cAMP-dependent agonists. In precontracted near-resistance pulmonary arteries, the addition of sildenafil reduced vasorelaxation response to NO donor S-nitroso-N-acetyl penicillamine (SNAP). A similar decrease in SNAP-induced vasodilation was observed in arteries pretreated with BAY 41-2272 (10 Ϫ9 M), a soluble guanylate cyclase stimulator cGMP, and its downstream protein kinase activator. cGMP also reduced the vasorelaxant response to the cAMPdependent forskolin. Inhibition of endogenous vascular NO generation enhanced SNAP-induced relaxation. The present data suggest that the mechanism involved in the cGMP desensitization to other relaxant agonists involves downregulation of the small heat shock protein HSP20 and is evident in rat pulmonary and systemic vascular smooth muscle cells. In newborn rats with chronic hypoxia-induced pulmonary hypertension, the combination of sildenafil and inhaled NO resulted in a lesser reduction in pulmonary vascular resistance compared with their individual effect. These data suggest that clinical exposure to one cGMP-dependent pulmonary vasodilator may affect the response to other cGMP-or cAMP-mediated agonists.sildenafil; nitric oxide; pulmonary hypertension; adenosine 3=,5=-cyclic monophosphate; guanosine 3=,5=-cyclic monophosphate THE SUCCESSFUL TRANSITION from fetal to postnatal life depends on a rapid decrease in pulmonary vascular resistance (PVR) at birth. The factors accounting for this dramatic reduction in PVR are incompletely understood, but nitric oxide (NO) is known to play an important role. The maintenance or recurrence of a high PVR postnatally characterizes the persistent pulmonary hypertension of the newborn syndrome (PPHN), a life-threatening condition requiring early and aggressive therapeutic interventions to improve and maintain adequate blood oxygenation (21).Inhaled NO is the standard of care to therapeutically promote pulmonary vasodilation in infants with PPHN, and significant clinical improvement is observed in many infants subjected to this therapy (2, 4). Yet, when response to inhaled NO is absent or partial, the clinical use of alternative agents with pulmonary vasodilatory properties may be contemplated (29).NO is endogenously generated by nitric...

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Section: Organ Bath Studiesmentioning

confidence: 99%

Section: Chronic Hypoxia-induced Rat Model Of Neonatal Pulmonary Hypementioning

confidence: 99%

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Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Enomoto

Jain

Pan

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…e causal role of ONOO − was demonstrated here, both by adding pure peroxynitrite (ONOO − ) and by using the ONOO − scavenger ebselen to block these responses [240]. Belik et al [241] asked whether hypoxia-caused PAH and vascular remodeling were caused by ONOO − elevation by using a ONOO − decomposition catalyst, FeTPPS. ey showed that FeTPPS blocked some but not other changes [241], showing that those that were blocked were probably produced by ONOO − .…”

Section: Peroxynitrite (Onoo −mentioning

confidence: 90%

“…Belik et al [241] asked whether hypoxia-caused PAH and vascular remodeling were caused by ONOO − elevation by using a ONOO − decomposition catalyst, FeTPPS. ey showed that FeTPPS blocked some but not other changes [241], showing that those that were blocked were probably produced by ONOO − . Masood et al [242] used this same FeTPPS decomposition catalyst to determine whether ONOO − was responsible for various changes in the pulmonary vasculature produced by 60% oxygen exposure in neonatal rats, leading to PAH.…”

Section: Peroxynitrite (Onoo −mentioning

confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pall

2013

ISRN Hypertension

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e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

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Pulmonary Arterial Hypertension and Oxidative Stress

Chrobak

Haeger

Maracle

et al. 2014

Oxidative Stress in Applied Basic Research and Clinical Practice

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Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats

Cited by 19 publications

References 25 publications

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pulmonary Arterial Hypertension and Oxidative Stress

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Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats

Cited by 19 publications

References 25 publications

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

Pulmonary Arterial Hypertension and Oxidative Stress

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Product

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Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review