Research Article Liraglutide Enhances the Activity of the ACE-2/Ang(1–7)/Mas Receptor Pathway in Lungs of Male Pups from Food-Restricted Mothers and Prevents the Reduction of SP-A J. Fandiño, A. A. Vaz, L. Toba, M. Romaní-Pérez, L. González-Matías, F. Mallo , and Y. Diz-Chaves Laboratory Endocrinology, LabEndo, Centro de Investigaciones Biomédicas (CINBIO), University of Vigo, E36310 Vigo, Spain Correspondence should be addressed to F. Mallo; fmallo@uvigo.es and Y. Diz-Chaves; yolandadiz@uvigo.es Received 30 April 2018; Accepted 30 July 2018; Published 2 December 2018 Academic Editor: Silvia Monticone Copyright © 2018 J. Fandiño et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In utero growth restriction and being born small for gestational age are risk factors for respiratory morbidity. IUGR (in utero growth retardation) is associated to overall reduction in lung weight, surfactant content and activity, impaired maturation of the alveolar type II cells, and decreased alveolar formation. The renin-angiotensin system (RAS) may be a key target underlying pathophysiological lung alterations. GLP-1 and agonists of its receptor modulate the expression levels of different components of RAS and also are very important for lung maturation and the production of surfactant proteins. The aim of this study was to elucidate the effects of IUGR induced by perinatal food restriction of the mother in the lung function of pups at early stages of life (PD21) and to determine if liraglutide had any effect during gestational period. Sprague-Dawley pregnant rats were randomly assigned to 50% food restriction (MPFR) or ad libitum control (CT) groups at day of pregnancy 12 (GD12). From GD14 to parturition, pregnant MPFR and CT rats were treated with liraglutide or vehicle. At postnatal day 21 and before weaning, 20 CT and 20 FR male pups were sacrificed and lungs were analyzed by RT-PCR. Liraglutide restored surfactant protein A (SP-A) mRNA expression in pup lungs from food-restricted mothers. Surfactant protein B (SP-B) mRNA expression is not affected by neither IUGR nor liraglutide treatment. Moreover, liraglutide modulated different elements of RAS, increasing angiotensin-converting enzyme 2 (ACE2) and MasR mRNA expression only in pups from food-restricted mothers (MPFR), despite food restriction had not any direct effect at this early stage. Liraglutide also increased endothelial nitric oxide synthase (eNOS) expression in MPFR lungs, reflecting the activation of MasR by angiotensin 1–7. In conclusion, liraglutide prevented the alteration in lung function induced by IUGR and promoted the positive effects of ACE2-Ang(1–7)-MasR in restoring lung function. 1. Introduction Lung development in mammals is initiated at embryogenesis (in rats begins about day 13, 13E); it continues through fetal development, and it is completed at postnatal life, from P7 to P21 in rats [1]. During fetal development, the cellular prolif- eration leads to the ramification pattern of the respiratory tree and drives the differentiation of many of cells including pulmonary epithelium. The type two (II) pneumocytes are the epithelial cells responsible of the synthesis and secretion of pulmonary surfactant, which consist in phospholipids (90%) and proteins (10%). The surfactant reduces surface tension in the interphase of the pulmonary alveoli preventing their collapse [2]. There are two types of surfactant proteins (SPs): hydrophilic SPs (SP-A and SP-D) and hydrophobic SPs (SP-B and SP-C) [3]. SP-A is the most abundant SP, and it maintains the pulmonary surfactant physicochemical stability and contributes to the in situ innate immune response [4]. SP-B is essential to respiratory function and when absent limits survival shortly after birth [5]. The appro- priate fetal pulmonary surfactant production is necessary for extrauterine life, and so any event affecting the production of surfactant proteins may delay lung maturation and compro- mise the postnatal respiratory function [6]. In humans, low weight at birth is a risk factor associated to impaired pulmonary function in the perinatal period [7] Hindawi International Journal of Endocrinology Volume 2018, Article ID 6920620, 9 pages https://doi.org/10.1155/2018/6920620