eNOS in rapid progressive pulmonary hypertension of the newborn

Endothelial nitric oxide synthase is upregulated in rapid progressive pulmonary hypertension of the newborn

Thomas Hoehn, Tony A Preston Alan R McPhaden, Brigitte Stiller, Martin Vogel, Christoph Bührer, Roger M Wadsworth

Introduction:

Rapid progressive pulmonary hypertension of the newborn (RPPHN) is characterized by abnormal hypertrophy of pulmonary arterioles and arteries leading to increased pulmonary vascular resistance. The underlying defect is still unknown, there is evidence for a dysbalance between pulmonary vascular constrictors and dilators.

Objective:

To provide evidence for the upregulation of the nitric oxide synthases eNOS (endothelial nitric oxide synthase) or iNOS (inducible nitric oxide synthase) in the assumed dysbalance in the pathophysiology of RPPHN. Furthermore to determine the cellular source and topographic distribution of eNOS and iNOS.

Material and Methods:

Lung biopsies were taken of two term neonates with clinical and echocardiographic evidence of rapid progressive pulmonary hypertension. Biopsies were obtained at an early stage of the disease as well as post mortem and examined immunohistochemically for eNOS, iNOS and nitrotyrosine. As control tissues served three paraffin-embedded, pulmonary postmortem samples of infants having died from sudden infant death syndrome (SIDS).

Results:

Endothelial cells of pulmonary arterioles stained significantly for eNOS protein in RPPHN patients, this was not the case in control infants. There were no differences for nitrotyrosine or iNOS between RPPHN-patients and controls.

Conclusion:

Rapid progressive pulmonary hypertension of the newborn leads to compensatory induction of eNOS-synthesis specifically in endothelial cells of pulmonary arterioles. This mechanism of compensation can lead to delayed presentation of RPPHN during late neonatal period. Exogenous iNO-therapy does not lead to suppression of endogenous synthesis of nitric oxide.

 

 

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