+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Oxidative and nitrosative stress in pediatric pulmonary hypertension: roles of endothelin-1 and nitric oxide

Oxidative and nitrosative stress in pediatric pulmonary hypertension: roles of endothelin-1 and nitric oxide

Vascular Pharmacology 45(5): 308-316

An increasing number of studies implicate oxidative stress in the development of endothelial dysfunction and the pathogenesis of cardiovascular disease. Further, this oxidative stress has been shown to be associated with alterations in both the endothelin-1 (ET-1) and nitric oxide (NO) signaling pathways such that bioavailable NO is decreased and ET-1 signaling is potentiated. However, recent data, from our groups and others, have shown that oxidative stress, ET-1, and NO are co-regulated in a complex fashion that appears to be dependent on the cellular levels of each species. Thus, when ROS levels are transiently elevated, NO signaling is potentiated through transcriptional, post-transcriptional, and post-translational mechanisms. However, in pediatric pulmonary hypertensive disorders, when reactive oxygen species (ROS) increases are sustained by ET-1 mediated activation of smooth muscle cell ET(A) subtype receptors, NOS gene expression and NO signaling are reduced. Further, increases in oxidative stress can stimulate both the expression of the ET-1 gene and the secretion of the ET-1 peptide. Finally, the addition of exogenous NO, and increasingly utilized therapy for pulmonary hypertension, can also lead to increases ROS generation via the activation of ROS generating enzymes and through the induction of mitochondrial dysfunction. Thus, this manuscript will review the available data regarding the interaction of oxidative and nitrosative stress, endothelial dysfunction, and its role in the pathophysiology of pediatric pulmonary hypertension. In addition, we will suggest avenues of both basic and clinical research that will be important to develop novel pulmonary hypertension treatment and prevention strategies, and resolve some of the remaining clinical issues regarding the use of NO augmentation.

(PDF emailed within 0-6 h: $19.90)

Accession: 012877318

Download citation: RISBibTeXText

PMID: 17049313

DOI: 10.1016/j.vph.2006.08.005

Related references

Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clinical Hemorheology and Microcirculation 37(1-2): 111-120, 2007

Adiponectin reduces carotid atherosclerotic plaque formation in ApoE-/- mice: roles of oxidative and nitrosative stress and inducible nitric oxide synthase. Molecular Medicine Reports 11(3): 1715-1721, 2015

Hypertension during vascular endothelial growth factor inhibition: focus on nitric oxide, endothelin-1, and oxidative stress. Antioxidants and Redox Signaling 20(1): 135-145, 2014

The chemical biology of nitric oxide Balancing niric oxide with oxidative and nitrosative stress. Mayer, Bernd Handbook of Experimental Pharmacology; Nitric oxide 7-29, 2000

Cytotoxicity related to oxidative and nitrosative stress by nitric oxide. Experimental Biology and Medicine 226(7): 621-623, 2001

Nitric oxide, oxidative stress and inflammation in pulmonary arterial hypertension. Journal of Hypertension 28(2): 201-212, 2010

Nitric oxide donors rescue diabetic nephropathy through oxidative-stress-and nitrosative-stress-mediated Wnt signaling pathways. Journal of Diabetes Investigation 6(1): 24-34, 2015

Endothelin-1 and nitric oxide metabolite levels in infants with persistent pulmonary hypertension treated with inhaled nitric oxide therapy. Pediatric Research 49(4 Part 2): 268A, 2001

Oxidative stress and persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide and different oxygen concentrations. Journal of Maternal-Fetal and Neonatal Medicine 25(9): 1723-1726, 2013

Levels of plasma endothelin, nitric oxide and atrial natriuretic peptide after cardiopulmonary bypass and influence of inhaled nitric oxide in patients with ventricular septal defect and pulmonary hypertension. Zhonghua Wai Ke Za Zhi 40(4): 290-293, 2002

N-acetylcysteine protects against diabetic nephropathy through control of oxidative and nitrosative stress by recovery of nitric oxide in rats. Nitric Oxide 78: 22-31, 2018

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi. American Journal of Reproductive Immunology 80(1): E12852, 2018

Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study. Bmc Pulmonary Medicine 15: 50, 2016

Bosentan inhibits oxidative and nitrosative stress and rescues occlusive pulmonary hypertension. Free Radical Biology and Medicine 56: 28-43, 2014

Nitric oxide reactivities of the two globins of the foodborne pathogen Campylobacter jejuni: roles in protection from nitrosative stress and analysis of potential reductants. Nitric Oxide 34: 65-75, 2014