Endothelin-1 and L-Arginine in Preterm Infants with Respiratory Distress Manal El Sayed, M.D., 1 Lobna Sherif, Ph.D., 2 Reem N. Said, M.D., 1 Amany S.E. El-Wakkad, M.D., 3 Amira EL-Refay, M.Sc., 2 and Hany Aly, M.D. 4 ABSTRACT In addition to the immaturity of air sacs and surfactant deficiency, preterm infants with respiratory distress syndrome (RDS) have abnormalities in the pulmonary vascular bed. We aimed to study two known modulators of pulmonary vessels: endothelin-1 (ET-1) and L-arginine. We hypothesized that plasma concentrations of ET-1 and L-arginine could correlate with the severity of RDS. We prospectively studied 71 preterm infants (gesta- tional age ¼ 29 to 35 weeks) with and without RDS. We measured plasma ET-1 by enzyme-linked immunosorbent assay and L-arginine by spectrophotometry. Infants who continued to require oxygen support or died by day of life 28 were considered to have bronchopulmonary dysplasia (BPD). ET-1 concentrations were significantly higher in RDS infants (p ¼ 0.039) than controls. Among infants with RDS, it was significantly higher in those who later developed BPD (p ¼ 0.026). L-arginine was significantly lower in RDS infants (p ¼ 0.001), but did not differ between BPD and non-BPD infants (p ¼ 0.19). There was no correlation between L-arginine and ET-1 (r ¼ 0.1, p ¼ 0.41). The acute phase of RDS is associated with increased plasma concentrations of ET-1 and decreased L-arginine. Infants who later developed BPD had higher plasma ET-1 at birth. Concen- trations of ET-1 and L-arginine did not correlate. KEYWORDS: Pulmonary vessels, nitric oxide, NO, surfactant, BPD, premature Respiratory distress syndrome (RDS) is the most common cause of respiratory failure and the leading cause in the pathogenesis of bronchopulmonary dyspla- sia (BPD) in premature infants. 1,2 Surfactant deficiency is considered the primary underlying cause of RDS in premature infants. 3 The administration of exogenous surfactant has shown immediate improvement in respi- ratory functions, whereas the incidence of BPD has not changed much for decades. 4,5 There has been a recent interest in the role of the pulmonary vascular bed in the pathogenesis of BPD. Recent trials demonstrated a significant clinical improvement when inhaled nitric oxide (NO), a known pulmonary vasodilator, was ad- ministered to preterm infants early in life before devel- oping any BPD. 6 Therefore, there is a genuine need to clearly understand the endothelial activities of the pul- monary vasculature in premature infants with RDS. Endothelin-1 (ET-1) is a 21-amino-acid peptide that has a potent vasoconstrictor property. It is secreted by endothelial cells and can be isolated in the human plasma. 7 In the respiratory system, ET-1 is synthesized by bronchial epithelial cells and stimulates bronchial subepithelial fibrosis and production of chemoattrac- tants for leukocytes. 8 ET-1 also possesses inflammatory 1 Department of Neonatology, Cairo University Children’s Hospital, Cairo, Egypt; Departments of 2 Child Health and 3 Medical Biochem- istry, National Research Center Cairo, Egypt; 4 Department of New- born Services, the George Washington University and Children’s National Medical Center, Washington, DC. Address for correspondence and reprint requests: Hany Aly, M.D., 900 23rd Street, NW, Suite G2092, Washington, DC 20037 (e-mail: haly@mfa.gwu.edu). Am J Perinatol 2011;28:129–136. Copyright # 2011 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. Received: March 5, 2010. Accepted after revision: June 15, 2010. Published online: August 10, 2010. DOI: http://dx.doi.org/10.1055/s-0030-1263295. ISSN 0735-1631. 129 Downloaded by: George Washington University. Copyrighted material.