Dibutyryl cAMP induces a gestation-dependent absorption of fetal lung liquid

1990 ◽  
Vol 68 (5) ◽  
pp. 2054-2059 ◽  
Author(s):  
D. V. Walters ◽  
C. A. Ramsden ◽  
R. E. Olver
Keyword(s):  
Fetal Lung ◽  
Liquid Volume ◽  
Intracellular Camp ◽  
Maximal Effect ◽  
Dibutyryl Camp ◽  
Rate Limiting Step ◽  
Liquid Absorption ◽  
Dependent Absorption ◽  
Lung Liquid ◽  
Rate Limiting

The maturation of the adenosine 3′,5′-cyclic monophosphate-(cAMP) dependent pathway controlling fetal lung liquid secretion was examined in experiments in which the lungs of chronically catheterized fetal lambs (123-141 days gestational age) were exposed to dibutyryl cAMP (DBcAMP, 10(-4) M). The effect of DBcAMP was markedly gestation dependent, with the greatest effect observed in the most mature fetuses. In immature fetuses (less than 130 days, mean age 125 days) DBcAMP caused slowing of secretion, with maximal effect at 5 h. With increasing maturity the effect of DBcAMP was more pronounced and occurred earlier so that in mature fetuses (mean age 140 days) lung liquid absorption took place, with maximal effect at 2 h. Changes in lung liquid volume flow induced by DBcAMP could be blocked by addition of 10(-4) M amiloride to lung liquid. It is concluded that 1) DBcAMP induces a change in lung liquid secretion that, like epinephrine, is mediated via an increase in Na+ permeability of the apical membrane of the lung epithelium and 2) the rate-limiting step in the maturation of this process must lie beyond the generation of intracellular cAMP.

Fetal breathing and pressures in the trachea and amniotic sac during oligohydramnios in sheep

1991 ◽  
Vol 70 (1) ◽  
pp. 293-299 ◽  
Author(s):  
K. A. Dickson ◽  
R. Harding
Keyword(s):  
Amniotic Fluid ◽  
Flow Rate ◽  
Pressure Fluctuations ◽  
Fetal Lung ◽  
Lung Hypoplasia ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Tracheal Pressure ◽  
Fetal Breathing ◽  
Lung Liquid

Oligohydramnios commonly leads to fetal lung hypoplasia, but the mechanisms are not fully understood. Our aim was to determine, in fetal sheep, the effects of prolonged oligohydramnios on the incidence and amplitude of tracheal pressure fluctuations associated with fetal breathing movements (FBM), on tracheal flow rate during periods of FBM (VtrFBM) and periods of apnea (Vtrapnea), on tracheal pressure relative to amniotic sac pressure, and on amniotic sac pressure relative to atmospheric pressure. In five sheep, oligohydramnios was induced by draining amniotic and allantoic fluids from 107 to 135 days of gestation (411.8 +/- 24.4 ml/day), resulting in fetal lung hypoplasia. In five control sheep, amniotic fluid volume was 732.3 +/- 94.4 ml. Oligohydramnios increased the incidence of FBM by 14% at 120 and 125 days and the amplitude of FBM by 30–34% at 120–130 days compared with controls. From 120 days onward, VtrFBM was 35–55% lower in experimental fetuses than in controls. Influx of lung liquid during FBM was 87% lower in experimental fetuses than in controls. Vtrapnea, tracheal pressure, and amniotic sac pressure were not significantly altered by oligohydramnios. Our tracheal flow rate data suggest that transient changes in lung liquid volume during periods of FBM and periods of apnea were diminished by oligohydramnios. We conclude that the primary factor in the etiology of oligohydramnios-induced lung hypoplasia is not an inhibition of FBM (as measured by tracheal pressure fluctuations) or a reduction in amniotic fluid pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Decline in lung liquid volume before labor in fetal lambs

1986 ◽  
Vol 61 (6) ◽  
pp. 2266-2272 ◽  
Author(s):  
K. A. Dickson ◽  
J. E. Maloney ◽  
P. J. Berger
Keyword(s):  
Regression Analysis ◽  
Flow Rate ◽  
Fetal Lung ◽  
Indicator Dilution ◽  
Liquid Volume ◽  
Confidence Limits ◽  
Least Squares Regression ◽  
Dilution Technique ◽  
Pulmonary Epithelium ◽  
Lung Liquid

The volume of liquid in the fetal lung depends on the amount of liquid secreted across the pulmonary epithelium and the amount flowing through the trachea. Lung liquid volume (V1) and secretion rate Vs) were determined using an indicator-dilution technique, while tracheal flow rate (Vtr) was measured simultaneously with a bubble flowmeter. Least-squares regression analysis showed that in 10 chronically instrumented fetal lambs, V1 increased from 51.0 ml at 119 days to 104.6 ml at 135 days (V1 = -347.65 + 3.35 X days; 95% confidence limits on slope: 1.89–4.81) before declining to 70.2 ml at 142 days gestation (V1 = 768.8 – 4.92 X days; 95% confidence limits on slope: -2.55 to -7.30). Similarly Vs increased from 7.4 ml/h at 119 days to 16.8 ml/h at 133 days (Vs = -72.35 + 0.67 X days; 95% confidence limits on slope: 0.21–1.14), before declining to 7.1 ml/h at 142 days (Vs = 159.07 – 1.07 X days; 95% confidence limits on slope: -0.56 to -1.57). Vtr did not change significantly with gestation. We conclude that V1 increases until 135 days gestation, after which it falls substantially. This fall in volume, which occurs well before the onset of labor, results predominantly from the decline in Vs.

Changes in lung expansion alter pulmonary DNA synthesis and IGF-II gene expression in fetal sheep

1993 ◽  
Vol 265 (4) ◽  
pp. L403-L409 ◽  
Author(s):  
S. B. Hooper ◽  
V. K. Han ◽  
R. Harding
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Mrna Levels ◽  
Pulmonary Tissue ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Expansion ◽  
Lung Liquid

Our aim was to determine the effect of short-term (7 days) alterations in fetal lung liquid volume on pulmonary DNA synthesis rates and insulin-like growth factor-II (IGF-II) mRNA levels. Fifteen chronically catheterized fetal sheep were divided into three groups. In one, the trachea was obstructed, in another lung liquid was drained by gravity, and the third group served as controls. After 7 days, [3H]thymidine was injected into each fetus and 8 h later fetal tissues were collected. Fetal lung-to-body weight ratios and total lung DNA contents were greatly increased in fetuses with tracheal obstruction compared with control fetuses, whereas the drainage of lung liquid did not affect these measurements. DNA synthesis rates in pulmonary tissue were significantly reduced from a mean control value of 153.3 +/- 25.1 disintegrations per minute (dpm)/microgram DNA to 57.2 +/- 8.6 dpm/microgram DNA by lung liquid drainage (P < 0.05) and were significantly increased to 236.0 +/- 24.0 dpm/microgram DNA by tracheal obstruction (P < 0.05). Following tracheal obstruction, lung IGF-II mRNA levels were increased to 177.0 +/- 18.2% (P < 0.05) of the mean value for control fetuses, whereas they were reduced to 56.1 +/- 7.1% of control in lung liquid-drained fetuses. We conclude that altering fetal lung expansion has a potent and rapid effect on pulmonary DNA synthesis and that this effect may, in part, be mediated by an alteration in IGF-II gene expression.

Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid

1995 ◽  
Vol 269 (4) ◽  
pp. R881-R887 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Plasma Cortisol ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Age Related ◽  
Lung Liquid ◽  
Secretion Rates ◽  
Related Increase

We have examined the role of cortisol in the gestational age-related increase in the ability of epinephrine to inhibit the secretion and induce the reabsorption of fetal lung liquid. Chronically catheterized fetal sheep were infused with either saline (n = 6) or increasing doses of cortisol (1.5-3.5 mg/day; n = 6) between 120 and 130 days of gestation (term approximately 145 days). Lung liquid volumes and secretion rates were measured at 120 days (before infusion) and at 125 days, and then at 130 days we tested the ability of epinephrine to inhibit lung liquid secretion and induce liquid reabsorption. Cortisol infusions increased fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentrations to levels observed just before labor and significantly increased the age-related increase in fetal lung liquid volume and secretion rate. At 130 days, epinephrine caused a significantly greater rate of lung liquid reabsorption in cortisol-infused fetuses (10.3 +/- 2.3 ml/h) than in saline-infused fetuses (1.5 +/- 1.6 ml/h). We conclude that a premature elevation in circulating fetal cortisol concentrations, probably in conjunction with elevated T3 concentrations, prematurely increases the epinephrine-induced reabsorption of fetal lung liquid. It is likely, therefore, that the preparturient increase of fetal cortisol concentrations plays an important role in the clearance of lung liquid at birth.

scholarly journals Cyclic 3', 5'-AMP relay in dictyostelium discoideum. IV. Recovery of the cAMP signaling response after adaptation to cAMP

1980 ◽  
Vol 86 (2) ◽  
pp. 545-553 ◽  
Author(s):  
M Dinauer ◽  
TL Steck ◽  
P Devreotes
Keyword(s):  
Time Course ◽  
Recovery Period ◽  
Camp Signaling ◽  
Intracellular Camp ◽  
Surface Receptors ◽  
First Order ◽  
Cellular Processes ◽  
First Order Kinetics ◽  
Rate Limiting Step ◽  
Rate Limiting

In dictyoselium discoideum, an increase in extracellular cAMP activates adenylate cyclase, leading to an increase in intracellular cAMP and the rate of cAMP secretion. Cells adapt to any constant cAMP stimulus after several minutes, but still respond to an increase in the concentration of the stimulus. We have now characterized the decay of adaptation (deadaptation) after the removal of cAMP stimuli. Levels of adaptation were established by the perfusion of [(3)H]adenosine-labeled amoebae with a defined cAMP stimulus. After a variable recovery period, the magnitude of the signaling response to a second stimulus was measured; its attenuation was taken as a measure of residual adaption to the first stimulus. The level of adaptation established by the first stimulus depended on both its magnitude and duration. Deadaptation began as soon as the first stimulus was removed. The magnitude of the response to the second stimulus increased with the recovery time in a first-order fashion, with a t(1/2)=3-4 min for stimuli of 10(-8) M to 10(-5) M cAMP. Responses to test stimuli, although reduced in magnitude, had an accelerated time-course when they closely followed a prior response that had not completely subsided. This effect is called priming; we believe it reveals a reversible, rate-limiting step that modulates the onset and termination of the signaling responses of amoebae that have not recently responded to a cAMP stimulus. We have suggested that the cAMP signaling response is controlled by two antagonistic cellular processes, excitation and adaptation. The data reported here imply that both the rate of rise in the adaptation process and the final level reached depend on the occupancy of cAMP surface receptors and that the decay of adaptation when external cAMP is removed proceeds with first-order kinetics.

Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep

1997 ◽  
Vol 82 (3) ◽  
pp. 927-932 ◽  
Author(s):  
A. Lines ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Production Rate ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Production Rates ◽  
Entire Volume ◽  
Fetal Sheep ◽  
Uterine Muscle ◽  
Near Term ◽  
Lung Liquid ◽  
Labor Onset

Lines, A., S. B. Hooper, and R. Harding. Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep. J. Appl. Physiol. 82(3): 927–932, 1997.—Previous studies have suggested that the volume and production rate of fetal lung liquid decrease late in gestation, before the onset of labor, in preparation for the clearance of lung liquid at birth. In contrast, our earlier studies have not shown a decrease in lung liquid volume near term, although these studies were not continued to the onset of labor. Our aim was to determine the changes in lung liquid volume and production rate in fetal sheep during the last 2 wk of gestation up to the onset of labor at term (∼147 days). In eight chronically catheterized fetal sheep, the volume and production rate of fetal lung liquid were measured at 130, 135, and 140 days of gestation and then on every 2nd day until the onset of labor. Labor was detected by monitoring uterine muscle activity and intrauterine pressure changes. On the day of labor onset, which occurred at 147 ± 1 days of gestation, fetuses weighed 5.0 ± 0.2 kg. The volume of fetal lung liquid was 40.4 ± 2.7 ml/kg at 19 ± 1 days before labor onset and had not significantly changed by 0.7 ± 0.2 days (44.8 ± 5.1 ml/kg) before labor. Similarly, lung liquid production rates at 19 ± 1 days before labor (5.1 ± 1.8 ml ⋅ h−1 ⋅ kg−1) were not significantly different from those at 0.7 ± 0.2 days before labor (3.4 ± 0.7 ml ⋅ h−1 ⋅ kg−1). We conclude that, in healthy ovine fetuses, lung liquid volumes and production rates do not decrease before the onset of labor. Our results indicate that the entire volume of fetal lung liquid (∼222.5 ± 36.6 ml) must be cleared after the onset of labor.

Fetal Lung Liquid Absorption during Epinephrine Infusion and Spontaneous Labor in the Lamb

CHEST Journal ◽  
1982 ◽  
Vol 81 (5) ◽  
pp. 65-66 ◽  
Author(s):  
D.V. Walters ◽  
C.A. Ramsden ◽  
M.J. Brown ◽  
R.E. Olver ◽  
L.B. Strang
Keyword(s):  
Fetal Lung ◽  
Epinephrine Infusion ◽  
Liquid Absorption ◽  
Lung Liquid

Effects of cAMP, its analogues, and forskolin on lung fluid production by in vitro lung preparations from fetal guinea pigs

1992 ◽  
Vol 70 (3) ◽  
pp. 330-337 ◽  
Author(s):  
Pawel M. Kindler ◽  
Sepideh Ziabakhsh ◽  
Anthony M. Perks
Keyword(s):  
Guinea Pigs ◽  
Fetal Lung ◽  
Dilution Method ◽  
Adenylate Cyclase System ◽  
Dibutyryl Camp ◽  
Lung Fluid ◽  
Fluid Production ◽  
High Doses ◽  
Lung Liquid

Lungs from fetal guinea pigs (62 ± 1 days of gestation) were supported in vitro for 3 h and fluid production was determined by a dye dilution method, based on Blue Dextran 2000. Twenty untreated lungs produced fluid at 1.41 ± 0.22 mL∙kg−1 body weight∙h−1, with no significant changes during later hours. Treatments with analogues of cAMP, cAMP, or forskolin during the middle hour reduced production significantly. Dibutyryl cAMP at 10−3 M produced reabsorption (117.8 ± 13.6% reduction, p < 0.001, n = 10); at 10−4 M it reduced production (77.3 ± 11.0% fall, p < 0.001, n = 10). 8-Bromo-cAMP appeared more effective; at 10−4 M it caused slight reabsorption (109.0 ± 8.9% reduction, p < 0.001, n = 6) and at lower concentrations it decreased production (at 10−6 M, 67.6 ± 9.6% fall, p < 0.001, n = 6; at 10−7 M, 40.0 ± 14.3% fall, p < 0.001, n = 6). At high doses, cAMP itself produced similar effects (at 5 × 10−3 M, 141.6 ± 22.8% reduction, p < 0.001, n = 6); at 10−4 it was ineffective (n = 3). Forskolin at 10−6 M induced the strongest reabsorptions seen (159.1 ± 10.9% reduction, p < 0.001, n = 6); at lower concentrations it reduced production (at 10−8 M, 73.8 ± 5.5% fall, p < 0.001, n = 6; at 10−9 M, 29.2 ± 9.2% fall, p < 0.05, n = 6). These results suggest a possible role for the adenylate cyclase system in the arrest of lung liquid production in the guinea pig around birth.Key words: cAMP, forskolin, fetal lung, lung fluid.

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