Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses.
*Gestational Age; *Hernias; Absorption; Amiloride/pharmacology; Animals; Body Fluids/*metabolism; Congenital; Diaphragmatic; Diaphragmatic/*metabolism; Epinephrine/metabolism; Epithelial Sodium Channels; Female; Fetal Organ Maturity; Fetus/*metabolism; Hernia; Male; Newborn; Phenyl Ethers/administration & dosage; Pregnancy; Propranolol/pharmacology; Rats; Respiratory System Abnormalities; Sodium Channels/metabolism; Sodium-Potassium-Exchanging ATPase/metabolism; Sprague-Dawley
We hypothesized that congenital diaphragmatic hernia (CDH) may decrease distal air space fluid absorption due to immaturity of alveolar epithelial cells from a loss of the normal epithelial Na+ transport, as assessed by amiloride and epithelial Na+ channel (ENaC) and Na-K-ATPase expression, as well as failure to respond to endogenous epinephrine as assessed by propranolol. Timed-pregnant dams were gavage fed 100 mg of nitrofen at 9.5-day gestation to induce CDH in the fetuses, and distal air space fluid absorption experiments were carried out on
Folkesson Hans G; Chapin Cheryl J; Beard LaMonta L; Ertsey Robert; Matthay Michael A; Kitterman Joseph A
American journal of physiology. Lung cellular and molecular physiology
2006
2006-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00124.2005" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00124.2005</a>
IL-1beta stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis.
Adrenocorticotropic Hormone/blood; Animals; Epinephrine/blood; Epithelial Sodium Channels; Extravascular Lung Water/*metabolism; Female; Guinea Pigs; Hydrocortisone/blood; Hypothalamo-Hypophyseal System/*physiology; Interleukin-1/blood/*pharmacology; Norepinephrine/blood; Pituitary-Adrenal System/*physiology; Pregnancy; Pulmonary Alveoli/*drug effects/embryology/*metabolism; Sodium Channels/metabolism; Sodium-Potassium-Exchanging ATPase/metabolism
We tested the hypothesis that interleukin (IL)-1beta-induced cortisol synthesis stimulates alveolar fluid clearance in preterm fetuses. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar 5% albumin in the lungs, and alveolar fluid movement was measured over 1 h from the change in alveolar protein concentration. Alveolar fluid clearance was induced at 61 days gestation and stimulated at 68 days gestation by IL-1beta, which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and cortisol concentrations were increased by IL-1beta at both gestational ages, and metyrapone reduced cortisol concentrations. IL-1beta was mostly low or undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance, when present as well as IL-1beta induced, was always propranolol and amiloride sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive Na+ channels were critical for fluid absorption. IL-1beta increased lung beta-adrenoceptor density at gestation day 61, and cortisol synthesis inhibition attenuated the increased beta-adrenoceptor density. Epithelial Na+ channel and Na+-K+-ATPase subunit expressions were both increased by IL-1beta and attenuated by cortisol synthesis inhibition. These results may explain why babies delivered preterm after intrauterine inflammation have a reduced risk of developing severe respiratory distress.
Ye Xin; Acharya Reshma; Herbert Jonathan B; Hamilton Sarah E; Folkesson Hans G
American journal of physiology. Lung cellular and molecular physiology
2004
2004-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00214.2003" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00214.2003</a>
Involvement of {alpha}ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis.
*RNA Interference; Absorption; Animals; Body Fluids/*metabolism; Death; Endosomal Sorting Complexes Required for Transport; Epithelial Sodium Channels/genetics/*physiology; Extravascular Lung Water/metabolism; Gene Silencing; Lung/*metabolism; Nedd4 Ubiquitin Protein Ligases; Newborn/*metabolism; Rats; RNA; Small Interfering/metabolism; Sodium-Potassium-Exchanging ATPase/metabolism; Sprague-Dawley; Tissue Distribution; Ubiquitin-Protein Ligases/genetics/metabolism/*physiology
To explore interactions between the epithelial Na channel (ENaC) and neural precursor expressed, developmentally downregulated protein 4-2 (Nedd4-2) at the conversion of the rat lung from fluid secretion to absorption at birth, we used small-interfering RNA (siRNA) against alphaENaC and Nedd4-2. siRNA-generating plasmid DNA (pDNA) was administered via trans-thoracic intrapulmonary (ttip) injection 24 h before ENaC and Nedd4-2 expression, extravascular lung water, and mortality were measured. alphaENaC mRNA and protein were specifically reduced by approximately 65% after pSi-4 injection. Nedd4-2 mRNA and protein were reduced by approximately 60% after pSi-N1 injection. Interestingly, alphaENaC and betaENaC mRNA and protein expression were increased after Nedd4-2 silencing. Extravascular lung water was significantly increased after alphaENaC silencing and reduced after Nedd4-2 silencing. alphaENaC silencing resulted in a fourfold increase in newborn mortality, whereas silencing Nedd4-2 did not affect mortality. We also isolated distal lung epithelial (DLE) cells after in vivo alphaENaC or Nedd4-2 silencing and measured alphaENaC or Nedd4-2 expression in freshly isolated DLE cells. In these DLE cells, there were attenuated alphaENaC or Nedd4-2 mRNA and protein, thus demonstrating that alphaENaC and Nedd4-2 silencing occurred in alveolar epithelial cells after ttip injection. We also looked for pDNA by PCR to determine pDNA presence in the lungs and found strong evidence for pDNA presence in both lungs. Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.
Li Tianbo; Koshy Shyny; Folkesson Hans G
American journal of physiology. Lung cellular and molecular physiology
2007
2007-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajplung.00151.2007" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00151.2007</a>
Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal volumes.
Time Factors; Animals; Gestational Age; Guinea Pigs; *Premature Birth; Phosphorylation; Enzyme Activation; Permeability; Extracellular Signal-Regulated MAP Kinases/metabolism; Intubation; Epithelial Sodium Channels/metabolism; Absorption; Sodium-Potassium-Exchanging ATPase/metabolism; Fetal Organ Maturity; Epinephrine/blood; Extravascular Lung Water/*metabolism; *Tidal Volume; Albumins/administration & dosage/*metabolism; Hydrocortisone/blood; Lung/embryology/*metabolism/physiopathology; MAP Kinase Kinase Kinases/metabolism; Ventilator-Induced Lung Injury/metabolism/physiopathology/*prevention & control; Newborn; Intratracheal; Artificial/adverse effects/*methods; Respiration
The objective of this study was to determine if low tidal volume (V(t)) ventilation was beneficial when ventilating preterm fetuses. The authors ventilated preterm guinea pig fetuses at gestation day (GD) 67, 3 days before birth, newborn, and 10-day-old (PD10) guinea pigs with low V(t) (6 mL/kg body weight [bw]) and compared them to age-matched fetuses/animals ventilated with higher potentially injurious V(t) (12 mL/kg bw). Lung fluid absorption was measured after intratracheal instillation of 5% albumin in 0.9% NaCl. Low V(t) ventilation stimulated lung fluid absorption when compared to higher V(t) in all groups. The increased lung fluid absorption in low V(t)-ventilated fetuses was associated with increased alpha epithelial Na channel (alphaEnaC) mRNA. However, alphaENaC and betaENaC protein was unchanged over the 1-hour study. Because stretch induces mitogen-activated protein (MAP) kinase expression and MAP kinases may affect lung fluid absorption, the authors investigated if MAP kinase (MAPK) expression was affected by V(t). Extracellular signal-regulated kinase (ERK) and MAPK/ERK kinase (MEK) were phosphorylated in the higher V(t)-ventilated guinea pig fetuses. This suggested that a reduced activation of MAP kinases might explain the increased lung fluid absorption in the low V(t)-ventilated fetuses. Thus these data suggest that low V(t) ventilation increases fetal lung fluid absorption and thus may be preferential to use clinically.
Koshy Shyny; Beard LaMonta L; Kuzenko Stephanie R; Li Tianbo; Folkesson Hans G
Experimental lung research
2011
2011-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3109/01902148.2010.514024" target="_blank" rel="noreferrer noopener">10.3109/01902148.2010.514024</a>