Journal article
Peroxynitrite mediates right-ventricular dysfunction in nitric oxide-exposed juvenile rats
Free radical biology & medicine, Vol.49(9), pp.1453-1467
2010
DOI: 10.1016/j.freeradbiomed.2010.08.007
PMID: 20708678
Abstract
Chronic pulmonary hypertension in infancy and childhood frequently culminates in right-ventricular (RV) failure and early death. Current management may include prolonged treatment with inhaled nitric oxide (iNO). Our objective was to examine the effects of iNO on established chronic hypoxic pulmonary hypertension in juvenile rats, a model of chronic neonatal pulmonary hypertension characterized by increased pulmonary vascular resistance, vascular remodeling (RV hypertrophy and arterial medial wall thickening), and significant RV dysfunction. Pups were exposed to air or hypoxia (13% O
2) from postnatal day 1 to 21 while receiving iNO (20
ppm) from day 14 to 21. In hypoxia-exposed animals, treatment with iNO decreased pulmonary vascular resistance, but did not augment RV output or reverse vascular remodeling. In addition, RV output was significantly reduced in air-exposed iNO-treated pups. Nitrotyrosine (a marker of peroxynitrite-mediated reactions), apoptosis, and expression of nitric oxide synthases 1 and 2 were increased in RV (but not left-ventricular) tissue from both air- and hypoxia-exposed pups treated with iNO. Concurrent treatment with a peroxynitrite decomposition catalyst (FeTPPS, 30
mg/kg/day, ip) prevented apoptosis and completely normalized RV output in iNO-exposed animals. Our results provide the first evidence that iNO may adversely impact the right ventricle through increased local generation of peroxynitrite.
Details
- Title: Subtitle
- Peroxynitrite mediates right-ventricular dysfunction in nitric oxide-exposed juvenile rats
- Creators
- Robert P Jankov - Clinical Integrative Biology, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaPatricia Lewis - Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, ON M5S 1B2, CanadaCrystal Kantores - Clinical Integrative Biology, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaJulijana Ivanovska - Clinical Integrative Biology, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaEmily Z Xu - Clinical Integrative Biology, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaTodd Van Vliet - Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, ON M5S 1B2, CanadaAlvin H Lee - Clinical Integrative Biology, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaA. Keith Tanswell - Division of Neonatology, Department of Paediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaPatrick J McNamara - Division of Neonatology, Department of Paediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.49(9), pp.1453-1467
- DOI
- 10.1016/j.freeradbiomed.2010.08.007
- PMID
- 20708678
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2010
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology; Internal Medicine
- Record Identifier
- 9984093482602771
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