Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy
| Autor: | Steven H. Abman, Julie W. Harral, Kyle N Powers, R. Blair Dodson, Kendall S. Hunter, Erica W. Mandell, Gregory J. Seedorf |
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| Rok vydání: | 2015 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Physiology Heart Ventricles Hypertension Pulmonary Pulmonary Artery Rats Sprague-Dawley Pathogenesis Afterload Pregnancy Physiology (medical) Internal medicine medicine.artery medicine Vitamin D and neurology Animals Vitamin D Lung Hypertrophy Right Ventricular business.industry Cell Biology medicine.disease Pulmonary hypertension Elastin Rats Surgery Endotoxins medicine.anatomical_structure Animals Newborn Bronchopulmonary dysplasia Pulmonary artery Respiratory Physiological Phenomena Call for Papers Vascular resistance Cardiology Female Vascular Resistance business |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 309:L1438-L1446 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00302.2015 |
| Popis: | High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins ( P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work ( P < 0.05 vs. control and ETX+vit D) and elastic potential energy ( P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA ( P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment. |
| Databáze: | OpenAIRE |
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