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

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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The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.2.r324 ◽

1993 ◽

Vol 264 (2) ◽

pp. R324-R330 ◽

Cited By ~ 3

Author(s):

H. G. Chen ◽

C. E. Wood

Keyword(s):

Arginine Vasopressin ◽

Adrenocorticotropic Hormone ◽

Fetal Sheep ◽

Arterial Pco2 ◽

Fetal Plasma ◽

Arterial Blood ◽

Arterial Ph ◽

Bilateral Vagotomy ◽

Pregnant Ewe

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.

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Regulation of bioactive and immunoreactive ACTH secretion by CRF and AVP in sheep fetuses

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.6.e1076 ◽

1995 ◽

Vol 269 (6) ◽

pp. E1076-E1082 ◽

Cited By ~ 3

Author(s):

T. J. Zehnder ◽

N. K. Valego ◽

J. Schwartz ◽

A. White ◽

J. C. Rose

Keyword(s):

Arginine Vasopressin ◽

Adrenocorticotropic Hormone ◽

Corticotropin Releasing Factor ◽

Acth Secretion ◽

Fetal Sheep

The purpose of this study was to determine the effects of corticotropin-releasing factor (CRF) or arginine vasopressin (AVP) on the secretion of bioactive adrenocorticotropic hormone (bACTH) and immunoreactive ACTH (iACTH), the latter being measured by radioimmunoassay and separate two-site immunoradiometric assays for ACTH-(1-39) and ACTH precursors. Experiments were performed on chronically catheterized fetal sheep at 0.70 (n = 9) and 0.90 (n = 8) gestation. Each fetus received a 15-min infusion of CRF, AVP, or saline on 3 consecutive days. Blood was obtained before and 15 and 60 min after the infusion began. CRF significantly increased iACTH at 15 (younger group) and 60 min (both groups). CRF significantly increased bACTH and the bACTH-to-iACTH ratio (bACTH/iACTH) in both groups at 15 and 60 min. AVP significantly increased iACTH, bACTH, and bACTH/iACTH in both groups at 15 min. In two subgroups (n = 4/subgroup), CRF significantly increased ACTH-(1-39) and ACTH precursors at 15 and 60 min. CRF increased the ratio of ACTH-(1-39) to ACTH precursors [ACTH-(1-39)/ACTH precursors] at 15 (younger group) and 60 min (both groups). AVP increased ACTH-(1-39), ACTH precursors, and ACTH-(1-39)/ACTH precursors in both groups at 15 min. These findings show that both CRF and AVP can stimulate the secretion of bACTH, ACTH-(1-39), and ACTH precursors at 0.70 and 0.90 gestation. The proportional increments in bACTH/iACTH and ACTH-(1-39)/ACTH precursors suggest that CRF and AVP evoke selective increases in bACTH and ACTH-(1-39).

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Effect of cortisol on vasopressin response to hypertonic saline in fetal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.4.r861 ◽

1989 ◽

Vol 257 (4) ◽

pp. R861-R865

Author(s):

T. L. Bennett ◽

J. C. Rose

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Partial Pressure ◽

Hypertonic Saline ◽

Arginine Vasopressin ◽

Positive Influence ◽

Serum Osmolality ◽

Base Line ◽

Fetal Sheep ◽

Cortisol Levels

To determine the effect of cortisol on vasopressin responses to hyperosmolality, we infused hypertonic saline (HS) (12 meq/kg NaCl) into nine chronically cannulated fetal sheep ranging from 110 to 132 days of gestation. The experiment was performed twice on each fetus, once during a continuous cortisol infusion and once during a vehicle infusion. Administration of HS resulted in a prompt increase in serum osmolality from 292.1 +/- 1.8 to 310.4 +/- 2.5 mosmol/kg. Decreases were seen in pH, partial pressure of O2, and hematocrit from 7.37 +/- 0.01 to 7.31 +/- 0.01, from 22.5 +/- 1.6 to 20.0 +/- 2.0 mmHg, and from 35.6 +/- 1.7 to 32.6 +/- 1.6, respectively. Mean arterial pressure increased from 41.3 +/- 1.4 to 48.9 +/- 2.0 mmHg (P less than 0.01). Arginine vasopressin (AVP) rose from base line after HS (P = 0.11 vehicle experiments, P = 0.04 cortisol experiments), and AVP responses were greater in the cortisol experiments than in the vehicle experiments (delta AVP = 21.9 +/- 10.9 vs. 3.1 +/- 0.9 pg/ml, P = 0.05). Also there was a correlation noted between differences in AVP response and cortisol levels (P less than 0.04). We conclude that cortisol exerts a positive influence on the AVP response to HS in fetal sheep.

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Hormonal and biophysical responses to acute hypoxemia in fetal sheep at 0.7–0.8 gestation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-232 ◽

1990 ◽

Vol 68 (12) ◽

pp. 1527-1532 ◽

Cited By ~ 22

Author(s):

Kozo Akagi ◽

John R. G. Challis

Keyword(s):

Eye Movements ◽

Arginine Vasopressin ◽

Adrenocorticotropic Hormone ◽

Minimal Change ◽

Fetal Sheep ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Biophysical Changes

We examined whether there was a minimal change in fetal arterial [Formula: see text] necessary to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol or to affect the incidence of breathing movements or eye movements in fetal sheep at 106–117 days of gestation. Fetal sheep were exposed to two levels of hypoxemia, mild (4.1 mmHg [Formula: see text] drop) (1 mmHg = 133.32 Pa) and moderate (8.4 mmHg [Formula: see text] drop), for 1 h without acidemia. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia. In moderate hypoxemia, there were significant increases of fetal adrenocorticotropic hormone and arginine vasopressin and decreased incidence of fetal breathing movements. However, there were no significant changes in cortisol or eye movements. We conclude that a fetal arterial [Formula: see text] drop of between 4.1 and 8.4 mmHg is necessary to elicit responses to hypoxemia in fetal sheep at 106–117 days of gestation in adrenocorticotropic hormone, arginine vasopressin, and fetal breathing movements, but this degree of hypoxemia does not cause changes in cortisol or fetal eye movements.Key words: fetal sheep, hypoxemia, adrenocorticotropic hormone, arginine vasopressin, cortisol, fetal breathing movements, fetal eye movements.

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Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-187 ◽

1987 ◽

Vol 65 (6) ◽

pp. 1186-1192 ◽

Cited By ~ 10

Author(s):

Laurie J. Norman ◽

John R. G. Challis

Keyword(s):

Negative Feedback ◽

Arginine Vasopressin ◽

Late Pregnancy ◽

Feedback Effect ◽

Plasma Acth ◽

Fetal Sheep ◽

Corticotrophin Releasing Factor ◽

Basal Release ◽

Sheep Fetus ◽

Acth Release

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113–116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126–130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma Cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or Cortisol response to oCRF, AVP, or oCRF + AVP at d 136–140, but dexamethasone suppressed basal ACTH and Cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113–116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and Cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly. Our results suggest different controls of basal and stimulated ACTH release from the pituitary at d 113–116 of gestation. Our findings would be consistent with the pituitary as a level of action for the negative feedback effect of corticosteroids on stimulated ACTH release throughout the last third of pregnancy in fetal sheep.

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Arginine vasopressin responses to hypoxia and hypercapnia in late-gestation fetal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.6.r1077 ◽

1991 ◽

Vol 260 (6) ◽

pp. R1077-R1081 ◽

Cited By ~ 6

Author(s):

H. Raff ◽

C. W. Kane ◽

C. E. Wood

Keyword(s):

Arginine Vasopressin ◽

Late Gestation ◽

Fetal Sheep ◽

Fetal Plasma ◽

Hypoxic Conditions ◽

Arterial Ph ◽

Hypercapnic Hypoxia ◽

Per Se ◽

Peripheral Arterial

The purpose of this study was to determine the interaction of hypoxia and hypercapnia in the control of arginine vasopressin (AVP) secretion in fetal sheep and to determine the role of the peripheral arterial chemoreceptors in that response. We measured the plasma AVP response to hypercapnia and/or hypoxia in catheterized intact or sinoaortic-denervated fetal sheep between 123 and 144 days of gestation. Ewes were exposed to the following inspired gases: two successive 30-min periods of normocapnic normoxia, 30 min of normocapnic normoxia followed by 30 min of normocapnic hypoxia, two successive 30-min periods of hypercapnic normoxia, or 30 min of hypercapnic normoxia followed by 30 min of hypercapnic hypoxia (i.e., asphyxia). Hypercapnia per se had no significant effect on fetal plasma AVP. Normocapnic hypoxia per se resulted in a significant increase in fetal plasma AVP. Although hypercapnia resulted in a significant acidemia, the decrease in arterial pH was more marked under hypoxic conditions. Hypercapnia/acidemia augmented the AVP response to hypoxia. Fetal sinoaortic denervation did not significantly attenuate any of the AVP responses. We conclude that hypercapnia augments the fetal AVP response to hypoxia and that the AVP response to neither normocapnic nor hypercapnic hypoxia is dependent on afferent information carried in the carotid sinus or aortic nerves.

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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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