title: Postnatal growth restriction augments oxygen-induced pulmonary hypertension in a neonatal rat model of bronchopulmonary dysplasia.
abstract: Prematurity and fetal growth restriction are risk factors for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). Neonatal rats develop PH and vascular remodeling when exposed to hyperoxia. We hypothesize that postnatal growth restriction (PNGR) due to under-nutrition increases the severity of PH induced by hyperoxia in neonatal rats.
  
  
  
  Pups were randomized at birth to litters maintained in room air or 75% oxygen (hyperoxia), together with litters of normal milk intake (10 pups) or PNGR (17 pups). After 14 d, right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricular plus septal weight) and PH by echocardiography. Lungs were analyzed by immunohistochemistry, morphometrics, western blotting, and metabolomics.
  
  
  
  Hyperoxia and PNGR each significantly increased pulmonary arterial pressure, RVH and pulmonary arterial medial wall thickness, and significantly decreased pulmonary vessel number. These changes were significantly augmented in pups exposed to both insults. Hyperoxia and PNGR both significantly decreased expression of proteins involved in lung development and vasodilation.
  
  
  
  PNGR induces right ventricular and pulmonary vascular remodeling and augments the effects of oxygen in neonatal rats. This may be a powerful tool to investigate the mechanisms that induce PH in low-birth-weight preterm infants with BPD.
authors: Department of Pediatrics, UC Davis Medical Center, Sacramento, California.
authors: Stephen
authors: S
authors: Wedgwood
authors: Department of Pediatrics, UC Davis Medical Center, Sacramento, California.
authors: Cris
authors: C
authors: Warford
authors: Department of Pediatrics, UC Davis Medical Center, Sacramento, California.
authors: Sharleen C
authors: SC
authors: Agvateesiri
authors: Department of Internal Medicine, Division of Cardiovascular Medicine, UC Davis Health System, Sacramento, California.
authors: Phung
authors: P
authors: Thai
authors: Department of Pediatrics, University at Buffalo, Buffalo, New York.
authors: Sara K
authors: SK
authors: Berkelhamer
authors: Department of Pediatrics, Northwestern University, Chicago, Illinois.
authors: Marta
authors: M
authors: Perez
authors: Department of Pediatrics, UC Davis Medical Center, Sacramento, California.
authors: Mark A
authors: MA
authors: Underwood
authors: Department of Hospitalist Medicine, Children's National Health System, Washington, DC.
authors: Robin H
authors: RH
authors: Steinhorn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D031204:Caloric Restriction / Q000009:adverse effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D048788:Growth and Development; D018496:Hyperoxia / Q000150:complications; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction