Journal article
Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats
Free radical biology & medicine, Vol.49(8), pp.1306-1314
2010
DOI: 10.1016/j.freeradbiomed.2010.07.021
PMID: 20688155
Abstract
Evidence implicates oxidative stress as playing a prominent role in the pathogenesis of pulmonary hypertension, to which peroxynitrite anion (ONOO
−) may make a major contribution. Hypothesizing that removal of ONOO
− would attenuate chronic neonatal pulmonary hypertension, we examined the effects of a ONOO
− decomposition catalyst (FeTPPS) on pulmonary arteries in vitro, on primary cultured pulmonary artery smooth muscle cell (PASMC) and cardiomyocyte survival and growth, and on central hemodynamics in rat pups exposed to hypoxia (13% O
2) for 7
days from birth. Daily FeTPPS (30
mg/kg ip) reduced lung nitrotyrosine content, attenuated vascular remodeling, and normalized pulmonary vascular resistance in hypoxia-exposed animals. FeTPPS attenuated proliferation and increased apoptosis of neonatal PASMCs in vitro. Isolated neonatal pulmonary arteries treated with FeTPPS showed reduced agonist-induced force development and enhanced endothelium-dependent and -independent relaxation, possibly via increased nitrate. However, we observed endothelial dysfunction, enhanced lung tissue phosphodiesterase 5 activity, and biventricular cardiac hypertrophy in air-exposed animals receiving FeTPPS. Further, in contrast to PASMCs, FeTPPS enhanced survival of newborn cardiomyocytes. We conclude that decomposition of ONOO
− with FeTPPS attenuates chronic hypoxia-induced pulmonary hypertension; however, it may negatively influence the modulation of normal pulmonary arterial relaxation function, cell survival, and growth.
Details
- Title: Subtitle
- Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats
- Creators
- Jaques Belik - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Danielle Stevens - Maastricht University, 6202 Maastricht, The NetherlandsJingyi Pan - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Brendan A.S McIntyre - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Crystal Kantores - Clinical Integrative Biology, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Julijana Ivanovska - Clinical Integrative Biology, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Emily Z Xu - Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8Christine Ibrahim - Clinical Integrative Biology, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Brian K Panama - Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8Peter H Backx - Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8Patrick J McNamara - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada M5S 1A8Robert P Jankov - Division of Neonatology, Department of Pediatrics, University of Toronto, Toronto, ON, Canada M5S 1A8
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.49(8), pp.1306-1314
- DOI
- 10.1016/j.freeradbiomed.2010.07.021
- PMID
- 20688155
- 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
- 9984093329502771
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