Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction

Cassin, S.; DeMarco, Vincent G.; Perks, A. M.; Kuck, H; Ellis, T. M.

doi:10.1152/jappl.1994.77.3.1445

Cited by 16 publications

(8 citation statements)

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“…Second, we typically instill at least 50% more blue dextran, which should be sufficient to saturate all binding sites; if all binding sites are saturated with tracer, accurate estimates of lung liquid production can be made since we calculate production rates not from absolute volumes but from relative changes in volume over time. Third, we (unpublished data) and others (11,12) have used both techniques for several years and have consistently found similar estimates of lung liquid production when comparing the two.…”

Section: Discussionsupporting

confidence: 67%

Selective type 5 phosphodiesterase inhibition alters pulmonary hemodynamics and lung liquid production in near-term fetal lambs

Dukarm¹,

Steinhorn²,

Russell³

et al. 2005

Journal of Applied Physiology

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Nitric oxide causes dilation of the pulmonary circulation and reduction in net lung liquid production in the fetal lamb, two critical perinatal events. Phosphodiesterase inhibition alone causes similar changes and also enhances the effects of nitric oxide. To better define the cyclic guanosine 5'-monophosphate (GMP) pathway in these events, we studied the effects of a specific phosphodiesterase inhibitor, E4021, on pulmonary arteries and veins isolated from near-term fetal lambs, as well as in intact, chronically instrumented late-gestation fetal lambs. In the in vitro experiments, both pulmonary arteries and veins relaxed to E4021 in a dose-dependent manner, although pulmonary veins were significantly more sensitive to E4021. Pretreatment with N(G)-nitro-l-arginine (L-NNA) abolished this response in arteries but not in veins. In both arteries and veins, pretreatment with beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate blunted relaxations to E4021. In the in vivo experiments, E4021 infusion into either the pulmonary artery or central venous circulation increased pulmonary blood flow and decreased pulmonary vascular resistance, and these responses were blunted by pretreatment with L-NNA. Net lung liquid production, measured by a dye-dilution technique using blue dextran, decreased when E4021 was infused directly into the pulmonary artery and this effect was not altered by L-NNA. There was no effect on lung liquid production when E4021 was infused into the central venous circulation. Taken together, these results suggest that the pulmonary hemodynamic effects of E4021 involve the cyclic GMP pathway and are primarily nitric oxide synthase dependent. In contrast, the effects on E4021 on net lung liquid production appear to be independent of nitric oxide synthase, suggesting that these two critical perinatal events might be modulated independently.

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Section: Discussionsupporting

confidence: 67%

Selective type 5 phosphodiesterase inhibition alters pulmonary hemodynamics and lung liquid production in near-term fetal lambs

Dukarm¹,

Steinhorn²,

Russell³

et al. 2005

Journal of Applied Physiology

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“…Previous studies have suggested that this results from an associated increase in Na + ,K + ‐ATPase expression, as well as an increase in the amiloride‐inhibitable Na + transporter ENaC. Cortisol increases lung liquid reabsoption in response to exogenous arginine vasopressin (AVP) infusion (Cassin et al 1994). However, it is possible that the increase in AQP expression plays an important role in mediating the cortisol‐induced increase in fetal lung secretion as well as the lung's increased ability to reabsorb liquid in response to adrenaline/AVP.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin gene expression and regulation in the ovine fetal lung

Liu

Hooper

Armugam

et al. 2003

The Journal of Physiology

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During fetal life, the future airways of the lung are filled with a liquid that plays a crucial role in the growth and development of the lungs by maintaining them in an expanded state. Lung liquid is secreted across the pulmonary epithelium into the lung lumen due to the osmotic gradient established by the net movement of Cl _ in the same direction. It is not known exactly when lung liquid secretion begins, but fluid is present by midgestation in fetal sheep and is secreted at 2-4 ml kg _1 h _1 between 120 days of gestation and term (~150 days). Fetal lung liquid exits the lungs via the trachea, whereby it is either swallowed (approximately 50 %) or passes directly into the amniotic sac, where it contributes to amniotic fluid volume (Harding & Hooper, 1999).If the fetal trachea is obstructed, which prevents the outward flow of lung liquid, the fetal lung expands with accumulated liquid. This is a potent stimulus for fetal lung growth and also greatly reduces the proportion of type-II alveolar epithelial cells (AECs). Lung liquid drainage on the other hand, deflates the lung, causes lung growth to cease, but increases the proportion of type-II AECs, possibly via type-I to type-II cell differentiation (Flecknoe et al. 2002). As a result it is now widely recognized that the degree to which the fetal lungs are expanded by lung liquid determines the growth and structural development of the lung, as well as the differentiated state of type-I and type-II AECs (Harding & Hooper, 1999). Despite the importance of lung liquid in the development of the lung, the factors controlling the movement of liquid across the pulmonary epithelium have not been fully explored. Furthermore, the effective clearance of lung liquid at birth is vital to allow the entry of air into the lungs with the onset of respiratory gas exchange. This process is largely dependent on the capability of the epithelium to reabsorb large quantities of water.Aquaporins (AQPs) are specific water channels that allow the rapid transcellular movement of water in response to osmotic/hydrostatic pressure gradients (King & Yasui, 2002). At least four AQPs (AQP1, 3, 4 and 5) are expressed in the lungs of various species, including humans, rats, mice and rabbits, although some discrepancies exist in the specific sites of distribution of these proteins. In all species described so far (human, rat, mouse), AQP1 is expressed in the apical and basolateral membrane of the microvascular endothelium and decreased pulmonary vascular permeability has been shown in AQP1-null humans . AQP3 is expressed in the basolateral membrane of basal cells of the tracheal epithelium and in submucosal gland cell membranes in rodents, but is also found in bronchioles (apical membrane) and type-II alveolar Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air-breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression be...

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“…Where the irrecoverable tracer is located proved impossible for us to determine for BD, because we could not demonstrate its presence in blood. Thus the statement that there is no BD measurable in blood in other studies (8,9,17,26) cannot be used as evidence that BD is confined entirely within the lung compartment. For RISA we established that radiolabel was present in fetal blood and a number of fetal and maternal tissues, including the thyroid, after RISA was added to the fetal lung liquid.…”

mentioning

confidence: 89%

Errors in estimating lung liquid volume in fetal lambs when using radiolabeled serum albumin and blue dextran

Pfister

Ramsden

Neil

et al. 1999

Journal of Applied Physiology

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Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or blue dextran (BD) as volume tracers. We tested the reliability of both tracers at 124 (G124) and 142 days of gestation (G142; term = G147) when the labels were employed simultaneously. We measured the proportion of label bound reversibly to the lung, or apparently lost from the lung compartment, by washing out the lung with saline and 5% albumin. At G124, volume estimates with the two labels were similar. At G142, the volume estimate with BD (36.3 +/- 8.7 ml/kg of body wt) was higher (P < 0. 05) than with RISA (22.3 +/- 3.5 ml/kg). This difference resulted from reversible binding of BD, because 5% albumin washout released 38.5 +/- 4.0% of the BD added at the start of the experiment but a lesser amount of RISA (9.8 +/- 0.7%; P < 0.05). At G142, when RISA was used alone, its reversible binding was 1.3 +/- 0.2%. Background absorbance increased during experiments, giving rise to an apparent increase in BD concentration. We conclude that RISA is an effective tracer for lung liquid volume determination in the fetal lamb, whereas our findings of substantial epithelial binding of BD and large changes in background absorbance demonstrate that, under the conditions of our experiments, BD is a poor tracer close to term.

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Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction

Cited by 16 publications

References 0 publications

Selective type 5 phosphodiesterase inhibition alters pulmonary hemodynamics and lung liquid production in near-term fetal lambs

Selective type 5 phosphodiesterase inhibition alters pulmonary hemodynamics and lung liquid production in near-term fetal lambs

Aquaporin gene expression and regulation in the ovine fetal lung

Errors in estimating lung liquid volume in fetal lambs when using radiolabeled serum albumin and blue dextran

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