Reactive oxygen species-reducing strategies improve pulmonary arterial responses to nitric oxide in piglets with chronic hypoxia-induced pulmonary hypertension

Candice D. Fike, Anna Dikalova, James C. Slaughter, M. R. Kaplowitz, Y. Zhang, Judy L. Aschner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aims: There are no effective treatments for chronic pulmonary hypertension in infants with cardiopulmonary disorders associated with hypoxia, such as those with chronic lung disease. These patients often have poor or inconsistent pulmonary dilator responses to inhaled nitric oxide (iNO) therapy for unknown reasons. One possible explanation for poor responsiveness to iNO is reduced NO bioavailability caused by interactions between reactive oxygen species (ROS) and NO. Our major aim was to determine if strategies to reduce ROS improve dilator responses to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), in resistance pulmonary arteries (PRAs) from a newborn piglet model of chronic pulmonary hypertension. Results: The dilation to SNAP was significantly impaired in PRAs from piglets with chronic hypoxia-induced pulmonary hypertension. ROS scavengers, including cell-permeable and impermeable agents to degrade hydrogen peroxide (H2O2), improved dilation to SNAP in PRAs from chronically hypoxic piglets. Treatment with agents to inhibit nitric oxide synthase and NADPH oxidase, potential enzymatic sources of ROS, also improved dilation to SNAP in PRAs from hypoxic piglets. Innovation: Our studies are the first to utilize a newborn model of chronic pulmonary hypertension to evaluate the impact of a number of potential therapeutic strategies for ROS removal on responses to exogenous NO in the vessels most relevant to the regulation of pulmonary vascular resistance (PRA). Conclusions: Strategies aimed at reducing ROS merit further evaluation and consideration as therapeutic approaches to improve responses to iNO in infants with chronic pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)1727-1738
Number of pages12
JournalAntioxidants and Redox Signaling
Volume18
Issue number14
DOIs
StatePublished - May 10 2013
Externally publishedYes

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Pulmonary Hypertension
Reactive Oxygen Species
Nitric Oxide
Penicillamine
Lung
Pulmonary Artery
Dilatation
Newborn Infant
Therapeutics
Pulmonary diseases
NADPH Oxidase
Nitric Oxide Synthase
Vascular Resistance
Hydrogen Peroxide
Biological Availability
Lung Diseases
Hypoxia
Chronic Disease
Innovation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Reactive oxygen species-reducing strategies improve pulmonary arterial responses to nitric oxide in piglets with chronic hypoxia-induced pulmonary hypertension. / Fike, Candice D.; Dikalova, Anna; Slaughter, James C.; Kaplowitz, M. R.; Zhang, Y.; Aschner, Judy L.

In: Antioxidants and Redox Signaling, Vol. 18, No. 14, 10.05.2013, p. 1727-1738.

Research output: Contribution to journalArticle

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