Regulation of lung liquid secretion by arginine vasopressin in fetal sheep

1990 ◽  
Vol 258 (1) ◽  
pp. R104-R111 ◽  
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.

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.

Acidaemia enhances the inhibitory effect of hypoxia on fetal lung liquid secretion in sheep

1996 ◽  
Vol 8 (3) ◽  
pp. 327 ◽  
Author(s):  
MJ Wallace ◽  
SB Hooper ◽  
GJ McCrabb ◽  
R Harding
Keyword(s):  
Fetal Lung ◽  
Inhibitory Effect ◽  
Secretion Rate ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Treatment Groups ◽  
Fetal Asphyxia ◽  
Lung Liquid ◽  
The Individual ◽  
Secretion Rates

Previous studies have shown that moderate fetal asphyxia reduces the secretion rate of fetal lung liquid. The present aim was to determine the relative effects of the individual components of asphyxia (hypoxia, hypercapnia and acidaemia) on lung liquid secretion in fetal sheep. Fetal hyperoxia was also studied to determine the extent to which lung liquid secretion is restricted by the relatively low fetal blood PO2. As each manipulation of fetal blood gas tensions and pH treatment produced alterations in more than one aspect of blood composition, data from all treatment groups were combined and a multiple analysis of variance was performed to determine the separate effects of PaO2, PaCO2, SaO2 and pHa. Lung liquid secretion rate was significantly reduced when mean PaO2 values were below 24.5 mmHg (range 12.9-24.3 mmHg). When PaO2 values below 24.5 mmHg occurred in combination with pHa values below 7.275 (range 6.934-7.268) the secretion rates were further reduced. Alterations in pHa alone or in PaCO2 had no significant effect. These results indicate that hypoxia is the principal factor responsible for the inhibition of lung liquid secretion during asphyxia and that acidaemia enhances this inhibition.

Role of the adrenal glands in the maturation of lung liquid secretory mechanisms in fetal sheep

1996 ◽  
Vol 270 (1) ◽  
pp. R33-R40 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Gestational Age ◽  
Adrenal Glands ◽  
Fetal Lung ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Age Related ◽  
Lung Liquid ◽  
Secretion Rates ◽  
Related Increase

Our aim was to determine the role of the fetal adrenal glands in the gestational age-related increase in the ability of epinephrine to induce the reabsorption of lung liquid. Fetal lung liquid volumes and secretion rates were measured in five chronically catheterized control and six bilaterally adrenalectomized (ADX) fetal sheep at approximately 5-day intervals from 120 to 144 days of gestation (term approximately 146 days). The ability of epinephrine to induce the reabsorption of fetal lung liquid was then determined on day 144. Fetal adrenalectomy prevented the preparturient increase in fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentration and significantly reduced the gestational age-related increase in fetal lung liquid volumes and secretion rates. Close to term (144 days), epinephrine infusions caused a significantly greater rate of lung liquid reabsorption in control (32.2 +/- 4.8 ml/h) compared with ADX (3.7 +/- 0.7 ml/h) fetuses. We conclude that the presence of the fetal adrenal glands is necessary for the age-related increase in 1) the lung liquid secretion rate and 2) the ability of the fetal lung to reabsorb liquid late in gestation. It is likely that cortisol is the active adrenal hormone involved, supporting the theory that cortisol plays a crucial role in the clearance of lung liquid at birth.

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

1993 ◽  
Vol 74 (1) ◽  
pp. 111-115 ◽  
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.

Changes in surfactant-associated protein mRNA profile in growth-restricted fetal sheep

1999 ◽  
Vol 276 (3) ◽  
pp. L459-L465 ◽  
Author(s):  
Robert Gagnon ◽  
Johnathan Langridge ◽  
Kevin Inchley ◽  
Jun Murotsuki ◽  
Fred Possmayer
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Plasma Cortisol ◽  
Fold Increase ◽  
Fetal Lung ◽  
Placental Insufficiency ◽  
Control Group ◽  
Fetal Sheep ◽  
Tissue Levels ◽  
Fetal Plasma

To test the hypothesis that chronic placental insufficiency resulting in fetal growth restriction causes an increase in fetal lung surfactant-associated protein (SP) gene expression, we embolized chronically catheterized fetal sheep ( n = 6) daily using nonradioactive microspheres in the abdominal aorta for 21 days (between 0.74 and 0.88 of gestation) until fetal arterial oxygen content was reduced by ∼40–50%. Control animals ( n = 7) received saline only. Basal fetal plasma cortisol concentration was monitored. At the end of the experiment, fetal lung tissues were collected, and ratios of tissue levels of SP-A, SP-B, and SP-C mRNA to 18S rRNA were determined by standard Northern blot analysis. Total DNA content of fetal lungs was reduced by 30% in the embolized group compared with control group ( P = 0.01). There was a 2.7-fold increase in fetal lung SP-A mRNA ( P< 0.05) and a 3.2-fold increase in SP-B mRNA ( P < 0.01) in the chronically embolized group compared with those in the control group. SP-A and SP-B mRNA tissue levels were highly correlated with the mean fetal plasma cortisol levels on days 20–21( r = 0.90, P < 0.01 for SP-A mRNA and r = 0.94, P < 0.01 for SP-B mRNA). SP-C mRNA tissue levels were not significantly affected by placental insufficiency. We conclude that fetal growth restriction due to placental insufficiency is associated with alterations in fetal lung SP, suggesting enhanced lung maturation that was highly dependent on the degree of increase in fetal plasma cortisol levels.

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

1993 ◽  
Vol 75 (5) ◽  
pp. 1925-1929 ◽  
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.

scholarly journals Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

2009 ◽  
Vol 296 (2) ◽  
pp. E300-E304 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Signal Transduction ◽  
Arginine Vasopressin ◽  
Plasma Cortisol ◽  
Pituitary Cell ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Inositol 1,4,5 Trisphosphate ◽  
Sheep Fetus

Corticotrophs in the fetal sheep become increasingly responsive to arginine vasopressin (AVP) in late gestation. We previously reported that this may be due in part to corresponding increases in signal transduction (inositol 1,4,5-trisphosphate, IP3). These ontogenic changes are prevented by hypothalamo-pituitary disconnection (HPD), which also prevents fetal plasma cortisol concentrations from increasing in late gestation. This led us to hypothesize that cortisol is involved in mediating the changes in pituitary responsiveness. HPD was performed on fetal sheep at 120 days gestational age (dGA). Half of the HPD fetuses were infused with cortisol for 3 days beginning at 135–137 dGA (HPD+C). The remaining HPD fetuses and a group of sham-operated control fetuses were infused with saline. Pituitary cells were isolated and cultured. After 48 h, a subset of cells was stimulated with 100 nM AVP for 2 h, and the medium was collected for ACTH analysis. Another subset of cells was stimulated with 100 nM AVP for 30 min, and the formation of IP3 was determined. Plasma cortisol concentrations increased rapidly within the first 6 h after infusion (5.2 ± 1.9 to 29.7 ± 4.9 ng/ml) but did not increase thereafter. Cells from HPD+C and sham-operated fetuses secreted significantly more ACTH than those from HPD fetuses (% increase from control: 33.0 ± 8.8%, 47.9 ± 10.6%, and 11.9 ± 2.4%, respectively). IP3 formation was significantly increased in cells from HPD+C and sham-operated compared with HPD fetuses (% increase from control: 17.7 ± 4.4%, 18.9 ± 4.3%, and 4.6 ± 1.5%, respectively). These findings support the idea that cortisol plays a role in mediating the increase in pituitary responsiveness to AVP in the late-gestation fetal sheep.

Cortisol pretreatment enhances the lung growth response to tracheal obstruction in fetal sheep

1997 ◽  
Vol 273 (6) ◽  
pp. L1126-L1131 ◽  
Author(s):  
Rochelle E. Boland ◽  
Laura Nardo ◽  
Stuart B. Hooper
Keyword(s):  
Intravenous Injection ◽  
Dna Content ◽  
Growth Response ◽  
Fetal Lung ◽  
Saline Infusion ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Liquid ◽  
Secretion Rates

We have investigated whether cortisol pretreatment of sheep fetuses will result in a greater liquid accumulation within the lung and a greater lung growth response to obstruction of the fetal trachea. Chronically catheterized fetal sheep received either 1) a cortisol infusion at an increasing dose (1.5–4.0 mg/day) from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation ( n = 4); 2) a saline infusion from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation ( n = 4); or 3) a saline infusion from days 118 to 127 of gestation with no period of tracheal obstruction (control; n = 4). Fetal tracheal pressures were measured from days 128 to 131 of gestation, whereas lung liquid secretion rates and volumes were measured on days 118, 128, and 131 of gestation. On day 131 of gestation, all fetuses were given an intravenous injection of [3H]thymidine and were killed 8 h later. Cortisol pretreatment increased the volume of liquid that accumulated within the fetal lung from 69.5 ± 4.1 to 96.1 ± 14.1 ml/kg after 3 days of tracheal obstruction. Similarly, cortisol pretreatment significantly enhanced the increase in lung DNA content from 257.4 ± 11.0 to 309.1 ± 16.3 mg/kg after 3 days of tracheal obstruction. We conclude that pretreatment of fetuses with cortisol increases the volume of liquid that accumulates after tracheal obstruction and, as a result, increases the fetal lung growth response to tracheal obstruction.

scholarly journals Influence of cortisol on adipose tissue development in the fetal sheep during late gestation

2003 ◽  
Vol 176 (1) ◽  
pp. 23-30 ◽  
Author(s):  
A Mostyn ◽  
S Pearce ◽  
H Budge ◽  
M Elmes ◽  
AJ Forhead ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gestational Age ◽  
Plasma Cortisol ◽  
Late Gestation ◽  
Protein Abundance ◽  
Tissue Development ◽  
Voltage Dependent Anion Channel ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Adipose Tissue Development

The present study examined the extent to which the late gestation rise in fetal plasma cortisol influenced adipose tIssue development in the fetus. The effect of cortisol on the abundance of adipose tIssue mitochondrial proteins on both the inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion channel (VDAC)) mitochondrial membrane, together with the long and short forms of the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal adipose tIssue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/day for 5 days) or saline was infused up to 127-130 days of gestation, and (ii) adrenalectomised and intact controls at between 142 and 145 days of gestation (term=148 days). UCP1 protein abundance was significantly lower in adrenalectomised fetuses compared with age-matched controls, and UCP1 was increased by cortisol infusion and with gestational age. Adrenalectomy reduced the concentration of the long form of PRLR, although this effect was only significant for the highest molecular weight isoform. In contrast, neither the short form of PRLR, VDAC protein abundance or leptin mRNA expression was significantly affected by gestational age or cortisol status. Fetal plasma triiodothyronine concentrations were increased by cortisol and with gestational age, an affect abolished by adrenalectomy. When all treatment groups were combined, both plasma cortisol and triiodothyronine concentrations were positively correlated with UCP1 protein abundance. In conclusion, an intact adrenal is necessary for the late gestation rise in UCP1 protein abundance but cortisol does not appear to have a major stimulatory role in promoting leptin expression in fetal adipose tIssue. It remains to be established whether effects on UCP1 protein are directly regulated by cortisol alone or mediated by other anabolic fetal hormones such as triiodothyronine.

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)

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