Pediatric pulmonary hypertension

Roles of endothelin-1 and nitric oxide

Stephen Matthew Black, Sanjiv Kumar, Dean Wiseman, Kandasamy Ravi, Stephen Wedgwood, Victor Ryzhov, Jeffrey R. Fineman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 ETA 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. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction 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.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalClinical Hemorheology and Microcirculation
Volume37
Issue number1-2
StatePublished - Jul 6 2007

Fingerprint

Endothelin-1
Pulmonary Hypertension
Nitric Oxide
Pediatrics
Oxidative Stress
Reactive Oxygen Species
Smooth Muscle Myocytes
Cardiovascular Diseases
Gene Expression
Lung
Peptides
Research
Genes

Keywords

  • Cell signaling
  • Enzyme inhibition
  • Gene expression
  • Pulmonary hypertension
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Hematology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Black, S. M., Kumar, S., Wiseman, D., Ravi, K., Wedgwood, S., Ryzhov, V., & Fineman, J. R. (2007). Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clinical Hemorheology and Microcirculation, 37(1-2), 111-120.

Pediatric pulmonary hypertension : Roles of endothelin-1 and nitric oxide. / Black, Stephen Matthew; Kumar, Sanjiv; Wiseman, Dean; Ravi, Kandasamy; Wedgwood, Stephen; Ryzhov, Victor; Fineman, Jeffrey R.

In: Clinical Hemorheology and Microcirculation, Vol. 37, No. 1-2, 06.07.2007, p. 111-120.

Research output: Contribution to journalArticle

Black, SM, Kumar, S, Wiseman, D, Ravi, K, Wedgwood, S, Ryzhov, V & Fineman, JR 2007, 'Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide', Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 111-120.
Black SM, Kumar S, Wiseman D, Ravi K, Wedgwood S, Ryzhov V et al. Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clinical Hemorheology and Microcirculation. 2007 Jul 6;37(1-2):111-120.
Black, Stephen Matthew ; Kumar, Sanjiv ; Wiseman, Dean ; Ravi, Kandasamy ; Wedgwood, Stephen ; Ryzhov, Victor ; Fineman, Jeffrey R. / Pediatric pulmonary hypertension : Roles of endothelin-1 and nitric oxide. In: Clinical Hemorheology and Microcirculation. 2007 ; Vol. 37, No. 1-2. pp. 111-120.
@article{31d48e246374456e98990e685c0f360d,
title = "Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide",
abstract = "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 ETA 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. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction 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.",
keywords = "Cell signaling, Enzyme inhibition, Gene expression, Pulmonary hypertension, Reactive oxygen species",
author = "Black, {Stephen Matthew} and Sanjiv Kumar and Dean Wiseman and Kandasamy Ravi and Stephen Wedgwood and Victor Ryzhov and Fineman, {Jeffrey R.}",
year = "2007",
month = "7",
day = "6",
language = "English (US)",
volume = "37",
pages = "111--120",
journal = "Clinical Hemorheology and Microcirculation",
issn = "1386-0291",
publisher = "IOS Press",
number = "1-2",

}

TY - JOUR

T1 - Pediatric pulmonary hypertension

T2 - Roles of endothelin-1 and nitric oxide

AU - Black, Stephen Matthew

AU - Kumar, Sanjiv

AU - Wiseman, Dean

AU - Ravi, Kandasamy

AU - Wedgwood, Stephen

AU - Ryzhov, Victor

AU - Fineman, Jeffrey R.

PY - 2007/7/6

Y1 - 2007/7/6

N2 - 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 ETA 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. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction 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.

AB - 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 ETA 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. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction 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.

KW - Cell signaling

KW - Enzyme inhibition

KW - Gene expression

KW - Pulmonary hypertension

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=34347337745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34347337745&partnerID=8YFLogxK

M3 - Article

VL - 37

SP - 111

EP - 120

JO - Clinical Hemorheology and Microcirculation

JF - Clinical Hemorheology and Microcirculation

SN - 1386-0291

IS - 1-2

ER -