Endothelial nitric oxide synthase (NOS) is upregulated in rapid progressive pulmonary hypertension of the newborn.
OBJECTIVE
To provide evidence for the upregulation of endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) in the assumed imbalance in the pathophysiology of rapid progressive pulmonary hypertension of the newborn (RPPHN), which is characterized by abnormal hypertrophy of the pulmonary arterioles and arteries leading to increased pulmonary vascular resistance. Furthermore, to determine the cellular source and topographic distribution of eNOS and iNOS.


METHODS
Lung biopsies were taken from two term neonates with clinical and echocardiographic evidence of RPPH and of three controls. Biopsies were obtained at an early stage of the disease as well as at post mortem and examined immunohistochemically for the presence of eNOS, iNOS and nitrotyrosine.


RESULTS
The endothelial cells of pulmonary arterioles stained significantly for eNOS protein in RPPHN patients. This was not the case in the control infants. There were no differences for nitrotyrosine or iNOS between RPPHN patients and controls.


CONCLUSIONS
Rapid progressive pulmonary hypertension of the newborn leads to compensatory induction of eNOS synthesis specifically in endothelial cells of the pulmonary arterioles. This mechanism of compensation can lead to delayed presentation of RPPHN during the late neonatal period. Exogenous inhaled nitric oxide therapy does not lead to suppression of the endogenous synthesis of nitric oxide.
Hoehn
Thomas
T
Department of Neonatology, Humboldt University, Charité Virchow Hospital, Augustenburger Platz 1, 13353 Berlin, Germany. thomas.hoehn@uni-duesseldorf.de
Preston
Anthony A
AA
McPhaden
Allan R
AR
Stiller
Brigitte
B
Vogel
Martin
M
Bührer
Christoph
C
Wadsworth
Roger M
RM
D004727:Endothelium / Q000166:cytology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation
D019001:Nitric Oxide Synthase