Nitric oxide synthases in infants and children with pulmonary hypertension and congenital heart disease

Thomas Hoehn,Roger M Wadsworth,Brigitte Stiller,Allan R Mcphaden

doi:10.1186/1465-9921-10-110

Abstract

RationaleNitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period.ObjectivesThe study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n = 26), compared to a control group who did not have pulmonary or cardiac disease (n = 8).MethodseNOS, iNOS and nNOS were identified by immunohistochemistry and quantified in specific cell types.Measurements and main resultsSignificant increases of eNOS and iNOS staining were found in pulmonary vascular endothelial cells of patients with congenital heart disease compared to control infants. These changes were confined to endothelial cells and not present in other cell types. Patients who strongly expressed eNOS also had strong expression of iNOS.ConclusionUpregulation of eNOS and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure.

Highlights

Nitric oxide (NO) plays a central role in the maintenance of normal pulmonary vascular tone and healthy lung function [1]
Upregulation of endothelial NOS (eNOS) and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure
Expression of eNOS was greatly increased in pulmonary hypertensive lungs compared to control lungs in the pulmonary artery endothelium (Figure 1, Figure 2)

Summary

Introduction

Nitric oxide (NO) plays a central role in the maintenance of normal pulmonary vascular tone and healthy lung function [1]. All 3 isoforms of nitric oxide synthase (NOS) are present in the lungs and contribute to NO production in specific cell types [2]. There is evidence from experimental models of neonatal pulmonary hypertension that impairment of NOS can generate reactive oxygen species, leading to a further cycle of deterioration of the vascular endothelium [4]. In adults with pulmonary arterial hypertension it has been demonstrated that output of NO is diminished [5], and that those patients who responded well to therapy had corresponding improve-. NO status can be improved by administration of inhaled NO which is valuable in the management of infants with pulmonary hypertension [710]

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Conclusion