Apelin Attenuates Hyperoxic Lung and Heart Injury in Neonatal Rats

作者：de Vissei Yvonne P; Walther Frans J; Laghmani El Houari; van der Laarse Arnoud; Wagenaar Gerry T M^*

来源：American Journal of Respiratory and Critical Care Medicine, 2010, 182(10): 1239-1250.

DOI：10.1164/rccm.200909.1361OC

• alveolarization
• bronchopulmonary dysplasia
• nitric oxide
• synthase inhibition
• lung inflammation
• right ventricular hypertrophy

Rationale Apelin, a potent vasodilator and angiogenic factor, may be a novel therapeutic agent in neonatal chronic lung disease, including bronchopulmonary dysplasia
Objectives To determine the beneficial effect of apelin in neonatal rats with hyperoxia induced lung injury, a model for premature infants with bronchopulmonary clysplasia
Methods The cardiopulmonary effects of apelin treatment (62 mu g/kg/d) were studied in neonatal rats by exposure to 100% oxygen, using two treatment strategies early concurrent treatment during con tinuous exposure to hyperoxia for 10 days and late treatment and recovery in which treatment was started on Day 6 after hyperoxic injury for 9 days and continued during the 9 day recovery period We investigated in both models the role of the nitric oxide cyclic guanosine monophosphate (cGMP) pathway in apelin treatment by specific inhibition of the nitric oxide synthase activity with N-omega nitro L arginine methyl ester (L NAME, 25 mg/kg/d)
Measurements and Main Results Parameters investigated include survival, lung and heart histopathology, pulmonary fibrin deposition and inflammation, alveolar vascular leakage, lung cGMP levels, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue Prophylactic treatment with apelin improved alveolarization and angiogenesis increased lung cGMP levels, and reduced pulmonary fibrin deposition, inflammation, septum thickness, arteriolar wall thickness, and right ventricular hypertrophy These beneficial effects were completely absent in the presence of c NAME In the injury recovery model apelin also improved alveolarization and angiogenesis, reduced arteriolar wall thickness, and attenuated right ventricular hypertrophy
Conclusions. Apelin reduces pulmonary inflammation, fibrin deposition, and right ventricular hypertrophy, and partially restores alveolarization in rat pups with neonatal hyperoxic lung Injury via a nitric oxide synthase-dependent mechanism

• 出版日期2010-11-15