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

The present studies were designed to test the hypothesis that arginine vasopressin (AVP) can interact with hydrocortisone and 3,5,3 ′-triiodothyronine (T3) to induce maturation of lung liquid reabsorptive processes in fetal sheep < 130 days gestation. Lung liquid production rates were measured in chronically catheterized thyroidectomized fetal sheep during eight different experimental treatments. Each experiment consisted of a 2-h control period followed by a 5-h treatment period. Net secretion or reabsorption of lung liquid was measured by using impermeant marker dilution techniques. AVP alone (50 mU/kg bolus plus 5.0 mU.kg-1.min-1 i.v. infusion) does not alter lung liquid secretion in fetal sheep 125 +/- 0.72 (SE) days gestation. In contrast, AVP (same dose as above) with T3 (30 micrograms) and hydrocortisone (6.94 mg/min) depressed lung liquid secretion and caused reabsorption of fluid. T3 alone, T3 and hydrocortisone, T3 and AVP, hydrocortisone alone, hydrocortisone and AVP, and saline did not result in net lung liquid reabsorption over a 5-h treatment period. These investigations demonstrate that AVP, T3, and hydrocortisone interact to cause lung liquid reabsorption in immature fetal lungs.

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Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.1.111 ◽

1993 ◽

Vol 74 (1) ◽

pp. 111-115 ◽

Cited By ~ 13

Author(s):

S. B. Hooper ◽

M. J. Wallace ◽

R. Harding

Keyword(s):

Control Period ◽

Fetal Lung ◽

Inhibitory Effect ◽

Luminal Surface ◽

Na Channels ◽

Inhibitory Effects ◽

Fetal Sheep ◽

Pulmonary Epithelial Cells ◽

Lung Liquid ◽

Secretion Rates

We have examined whether the activation of Na+ channels, located on the luminal surface of pulmonary epithelial cells, mediates the inhibitory effects of both arginine vasopressin (AVP) and moderate asphyxia on fetal lung liquid secretion. Lung liquid secretion rates were measured in chronically catheterized fetal sheep during AVP infusions and during periods of asphyxia with and without an Na+ transport blocker (amiloride; 10(-4) M) present in lung liquid. Lung liquid secretion rates were also measured during epinephrine infusions with amiloride present in lung liquid. These secretion rates were compared with measurements made during a preceding control period. Both asphyxia and an infusion of AVP significantly reduced the rate of secretion of fetal lung liquid from 8.4 +/- 1.5 and 18.0 +/- 3.7 to 3.6 +/- 1.0 (P < 0.01) and 5.5 +/- 2.1 ml/h (P < 0.01), respectively. The addition of amiloride to lung liquid did not reverse the inhibitory effects of asphyxia on lung liquid secretion (8.6 +/- 0.8 vs. 0.7 +/- 0.4 ml/h) but did block the inhibitory effects of both epinephrine (14.8 +/- 4.4 vs. 13.8 +/- 3.1 ml/h) and AVP (18.0 +/- 3.7 vs. 19.5 +/- 5.0 ml/h). The addition of amiloride to lung liquid during fetal normoxia did not significantly affect fetal lung liquid secretion rates (8.2 +/- 1.1 vs. 7.4 +/- 0.7 ml/h). We conclude that the inhibitory effect of AVP on fetal lung liquid secretion, like that of epinephrine, involves the activation of luminal surface Na+ channels, whereas the inhibitory effect of asphyxia does not.

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Regulation of lung liquid secretion by arginine vasopressin in fetal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.1.r104 ◽

1990 ◽

Vol 258 (1) ◽

pp. R104-R111 ◽

Cited By ~ 4

Author(s):

M. J. Wallace ◽

S. B. Hooper ◽

R. Harding

Keyword(s):

Gestational Age ◽

Arginine Vasopressin ◽

Plasma Cortisol ◽

Fetal Lung ◽

Inhibitory Effect ◽

Fetal Sheep ◽

Fetal Plasma ◽

Fetal Asphyxia ◽

Lung Liquid ◽

Secretion Rates

We have investigated the influence of gestational age on the inhibition of fetal lung liquid secretion by arginine vasopressin (AVP). In eight fetal sheep, lung liquid secretion rates were measured before and during infusion of AVP (300 mu.kg-1.h-1) at gestational ages between 110 and 148 days. During infusions, the concentration of AVP in fetal plasma increased from less than 8.7 +/- 0.2 pg/ml to 848.7 +/- 75.1 pg/ml. Fetal plasma epinephrine concentrations were not altered during AVP infusion. Infusions of AVP had no effect on fetal lung secretion before 135 days of gestation; they caused a 40.8% inhibition between 136 and 140 days, and at ages greater than 140 days induced an inhibition of 78.4%. In two ewes during labor, AVP infusion caused either a complete inhibition of secretion or reabsorption of lung liquid. The inhibitory effect of AVP increased in an exponential-like fashion with increasing gestational age and appeared to parallel the preparturient rise in fetal plasma cortisol concentrations. Our results indicate that AVP may be involved in the clearance of lung liquid at term and that AVP is unlikely to mediate the inhibitory effect of fetal asphyxia on lung liquid secretion, at least until after 135 days of gestation.

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

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.3.927 ◽

1997 ◽

Vol 82 (3) ◽

pp. 927-932 ◽

Cited By ~ 32

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.

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Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid secretion

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.5.1925 ◽

1993 ◽

Vol 75 (5) ◽

pp. 1925-1929 ◽

Cited By ~ 23

Author(s):

S. Cassin ◽

A. M. Perks

Keyword(s):

Arginine Vasopressin ◽

Fetal Lung ◽

Secretion Rate ◽

Tracer Technique ◽

Fetal Sheep ◽

Indwelling Catheters ◽

Lung Fluid ◽

Lung Liquid

The effects of arginine vasopressin (AVP) and amiloride were studied in 16 unanesthetized fetal sheep (129–135 days of age) with indwelling catheters. Secretion was measured by an impermeant tracer technique. Control fetuses showed no change in lung liquid secretion over a 5-h period with an average secretion rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1) in seven fetuses (134–140 days of age) produced significant decreases (from control) in the secretion rate over a 5-h period: the secretion rate decreased by 68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP, but after AVP effects had taken place, reversed the AVP-induced decrease in lung liquid secretion. AVP in conjunction with other hormones that are elevated during the stress of birth (epinephrine and cortisol) may be important in the removal of lung fluid at birth.

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Arginine Vasopressin Metabolie Clearance and Production Rates in Fetal Sheep, Pregnant Ewes, and Lambs

Developmental Pharmacology and Therapeutics ◽

10.1159/000457149 ◽

1984 ◽

Vol 7 (2) ◽

pp. 87-93 ◽

Cited By ~ 5

Author(s):

Hendrik Stegner ◽

Rosemary D. Leake ◽

Sue M. Palmer ◽

Anne Marie Morris ◽

Delbert A. Fisher

Keyword(s):

Arginine Vasopressin ◽

Production Rates ◽

Fetal Sheep

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Nitric oxide decreases lung liquid production in fetal lambs

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.5.1538 ◽

1997 ◽

Vol 83 (5) ◽

pp. 1538-1544 ◽

Cited By ~ 22

Author(s):

James J. Cummings

Keyword(s):

Nitric Oxide ◽

Control Period ◽

Isotonic Saline ◽

Fetal Lung ◽

Similar Reduction ◽

Pulmonary Hemodynamics ◽

Fetal Sheep ◽

Before And After ◽

Pulmonary Arterial ◽

Lung Liquid

Cummings, James J. Nitric oxide decreases lung liquid production in fetal lambs. J. Appl. Physiol. 83(5): 1538–1544, 1997.—To examine the effect of nitric oxide on fetal lung liquid production, I measured lung liquid production in fetal sheep at 130 ± 5 days gestation (range 122–137 days) before and after intrapulmonary instillation of nitric oxide. Thirty-one studies were done in which net lung luminal liquid production ( Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. To see whether changes in Jv might be associated with changes in pulmonary hemodynamics, pulmonary and systemic pressures were measured and left pulmonary arterial flow was measured by an ultrasonic Doppler flow probe. Variables were measured during a 1- to 2-h control period and for 4 h after a small bolus of isotonic saline saturated with nitric oxide gas (10 or 100%) was instilled into the lung liquid. Control (saline) instillations ( n = 6) caused no change in any variable over 6 h. Nitric oxide instillation significantly decreased Jv and increased pulmonary blood flow; these effects were sustained for 1–2 h. There was also a significant but transient decrease in pulmonary arterial pressure. Thus intrapulmonary nitric oxide causes a significant decrease in lung liquid and is associated with a decrease in pulmonary vascular resistance. In a separate series of experiments either amiloride or benzamil, which blocks Na+transport, was mixed into the lung liquid before nitric oxide instillation; still, there was a similar reduction in lung liquid production. Thus the reduction in lung liquid secretion caused by nitric oxide does not appear to depend on apical Na+ efflux.

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Effect of indomethacin on fetal lung liquid formation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-027 ◽

1984 ◽

Vol 62 (1) ◽

pp. 157-159 ◽

Cited By ~ 7

Author(s):

Sidney Cassin

Keyword(s):

Fetal Lung ◽

Dilution Technique ◽

Production Rates ◽

Fetal Sheep ◽

Blue Dextran ◽

Dye Dilution ◽

Lung Liquid ◽

Liquid Formation

Experiments were performed on seven anesthetized fetal sheep to evaluate involvement of metabolites of the cyclooxygenase system in lung liquid production. Rates of lung liquid production were determined by dye dilution technique using blue dextran. The control rate of formation of lung liquid in these preparations was 4.6 ± 0.55 mL∙kg−1∙h−1. Administration of indomethacin (1.85 mg/kg) intraarterially to fetuses resulted in a 60% decrease in the rate of formation of lung liquid. The present studies suggest an involvement of products of the cyclooxygenase system in controlling the rate of secretion of lung liquid in fetal animals.

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Nitric oxide decreases lung liquid production via guanosine 3′,5′-cyclic monophosphate

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.5.l923 ◽

2001 ◽

Vol 280 (5) ◽

pp. L923-L929 ◽

Cited By ~ 6

Author(s):

James J. Cummings ◽

Huamei Wang

Keyword(s):

Nitric Oxide ◽

Pulmonary Epithelium ◽

Fetal Sheep ◽

Cgmp Analog ◽

Pulmonary Arterial ◽

Series Of Experiments ◽

Lung Liquid ◽

Tracer Dilution ◽

Induced Changes

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ( J v ) in chronically instrumented fetal sheep. Forty-five studies were done in which J v was measured by a tracer dilution technique. Left pulmonary arterial flow (Qlpa) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased Qlpa but had no effect on J v. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Qlpa but significantly reduced J v. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on J v. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium.

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Intramembranous absorption rate is unaffected by changes in amniotic fluid composition

AJP Renal Physiology ◽

10.1152/ajprenal.00407.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. F964-F968 ◽

Cited By ~ 17

Author(s):

D. Anderson ◽

Q. Yang ◽

A. Hohimer ◽

J. Faber ◽

G. Giraud ◽

...

Keyword(s):

Amniotic Fluid ◽

Flow Measurement ◽

Control Period ◽

Ringer Solution ◽

Urine Flow ◽

Fluid Composition ◽

Fetal Sheep ◽

Urine Production ◽

Blood Pressures ◽

Vascular Catheters

Experiments were performed to determine the effect of amniotic fluid dilution on the rate of intramembranous absorption. Seven fetal sheep at 118 days gestation were instrumented with a shunt between the trachea and esophagus and arterial and venous vascular catheters. In addition, the urachus of the fetal bladder was ligated, and a catheter was placed in the bladder. Ligation of the urachus does not interfere with urine flow into the amnion. After 5 days of recovery, fetuses were randomly assigned to one of two protocols; all fetuses completed both protocols. In the fetuses in the control period, continuous urine flow measurement was begun. In the fetuses assigned to the isovolumic dilution protocol, continuous urine flow measurement was also begun and, in addition, amniotic fluid was continually exchanged with lactated Ringer solution on an isovolumic basis. After 3–4 days, fetal blood pressures and amniotic fluid volumes were determined. Amniotic fluid volumes were determined by drainage. Each fetus was then assigned to the remaining protocol. The presence of the tracheal-esophageal shunt and the ligation of the urachus allowed the rate of intramembranous absorption to be calculated. Isovolumic exchange showed no effect on fetal vascular pressures, blood-gas values, or urine production. We could demonstrate no effect of isovolumic dilution of amniotic fluid on its volume. However, we were able to demonstrate an inverse relationship between amniotic fluid volume and intramembranous absorption ( P < 0.02).

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