Ventilation-induced changes correlate to pulmonary vascular response and VEGF, VEGFR-1/2, and eNOS expression in the rat model of postnatal hypoxia

Author(s)

Figueira, R. L. ; Goncalves, F. L. ; Prado, A. R. ; Ribeiro, M. C. ; Costa, K. M. ; Castro e Silva, O. ; Sbragia, L.

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 51, n. 11, p. 8-pg., 2018-01-01.

Abstract

Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P < 0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P < 0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia. (AU)

• FAPESP's process: 12/09951-5 - Evaluation of nitric oxide in experimental model of neonatal asphyxia in ventilated rats
• Grantee: Maíra Cristina Ribeiro Andrade
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 11/12587-0 - Evaluation in vivo of the effect of corticosteroids and ventilation in oxide nitric pathway on the expression of VEGF and its pulmonary receptors after fetal tracheal occlusion in the congenital diaphragmatic hernia in rats
• Grantee: Frances Lilian Lanhellas Gonçalves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral