Dexamethasone-induced changes in lung function are not prevented by concomitant treatment with retinoic acid.
Alveolarization is impaired in rats treated with dexamethasone (Dex) on postnatal days 4-13, but concomitant treatment with all-trans retinoic acid (RA) increases alveolar number. To determine whether morphological changes induced by Dex and/or RA predict changes in lung function at 1 mo, we assessed resting breathing parameters, dynamic compliance, ventilation required to maintain O(2) saturation at > or = 90%, and pressure-volume curves of air-filled lungs. During resting breathing, mean tidal volume per gram was greater in Dex + RA-treated rats than in controls (P < 0.05). Dynamic compliance was also greater in Dex- and Dex + RA-treated rats than in controls or RA-treated rats (P < 0.02). In Dex- and Dex + RA-treated rats, we observed increased hysteresis ratios (P < or = 0.006), air trapping (P < 0.05), and lung volumes at 5 and 13.5 cmH(2)O pressure (P < 0.001) and decreased elastic recoil (P < 0.007). The effect of Dex on elastic recoil was greater in female than in male rats (P = 0.006). Despite impaired septation, O(2) saturation was not compromised in Dex- or Dex + RA-treated rats. Thus lung function changes induced by Dex treatment during alveolarization were not prevented by concomitant treatment with RA.
Department of Pediatrics, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.
Ganesh
G
Srinivasan
Eugene N
EN
Bruce
Pamela K
PK
Houtz
Margaret C
MC
Bruce
D000287:Administration, Topical; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids; D008168:Lung / Q000187:drug effects* / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects; D008176:Lung Volume Measurements; D008297:Male; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012146:Rest; D014212:Tretinoin / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D014212:Tretinoin; D003907:Dexamethasone