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PMID: 22401856 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Reactive oxygen and nitrogen species in pulmonary hypertension.

Free radical biology & medicine ·Vol. 52 ·No. 9 ·2012-05-01 ·Pages 1970-86

Tabima DM, Frizzell S, Gladwin MT

Abstract

Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right-heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5000 patients in the United States, the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS), and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of antiapoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This paper will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies for this disease.

MeSH Terms
Animals Humans Hypertension, Pulmonary/metabolism Reactive Nitrogen Species/metabolism Reactive Oxygen Species/metabolism
Chemicals
Reactive Nitrogen Species Reactive Oxygen Species
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tabima Diana M
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Frizzell Sheila
Gladwin Mark T
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Article Info
Journal
Free radical biology & medicine
Abbr.
Free Radic Biol Med
ISSN
1873-4596
DOI
10.1016/j.freeradbiomed.2012.02.041
Published
2012-05-01
Epub
2012-00-06
Pages
1970-86
Language
English
Region
United States
NLM ID
8709159
PMCID
PMC3856647
Subset
IM
Grants
NHLBI NIH HHS · P01 HL103455 · United States
NIDDK NIH HHS · RC1 DK085852 · United States
NHLBI NIH HHS · R01 HL098032 · United States
NHLBI NIH HHS · R01HL098032 · United States
NHLBI NIH HHS · R01 HL096973 · United States
NHLBI NIH HHS · R01HL096973 · United States
NHLBI NIH HHS · P01HL103455 · United States
NIDDK NIH HHS · RC1DK085852 · United States
External Links
PubMed source DOI: 10.1016/j.freeradbiomed.2012.02.041 PMC Full Text View journal details
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