Renal, hormonal, and cardiovascular responses to chronic angiotensin I infusion in the ovine fetus

1997 ◽  
Vol 272 (6) ◽  
pp. R1912-R1917 ◽  
Author(s):  
K. M. Moritz ◽  
K. Tangalakis ◽  
E. M. Wintour

Long-term infusion of angiotensin I (ANG I) into the ovine fetus has been shown to cause excess accumulation of fetal fluid in the allantoic compartment. It was hypothesized that this resulted from sustained increases in fetal urine production, and the hormonal basis was examined. ANG I (6.7 micrograms/h, n = 6) or isotonic saline (n = 6) was infused for 3 days into chronically cannulated ovine fetuses (112-122 days of gestation). ANG I caused an immediate and progressive increase in mean arterial blood pressure (from 42 +/- 2 to 57 +/- 4 mmHg), increased urine flow rate (from 15 +/- 3 to 48 +/- 8 ml/h), and increased glomerular filtration rate (from 97 +/- 15 to 146 +/- 24 ml/h), without significant changes in fetal plasma concentrations of aldosterone, atrial natriuretic factor (ANF), adrenocorticotropin, or cortisol. There were substantial increases in sodium and chloride excretion, due to both increased fetal urine concentrations and fetal urine flow, without significant changes in urine osmolality (from 134 +/- 9 to 147 +/- 12 mosmol/kg water). There were no significant changes in any parameter in the saline-infused fetuses. Neither amniotic or allantoic fluid volume was significantly changed by ANG I infusion, but allantoic fluid Cl- concentration increased significantly. The conclusions are that ANG I caused a diuresis and natriuresis in the fetal sheep independent of changes in cortisol or ANF.

1990 ◽  
Vol 258 (2) ◽  
pp. R469-R475
Author(s):  
L. K. Miner ◽  
R. A. Brace ◽  
C. Y. Cheung

The fetal urine flow response to acute increases in osmolality may be mediated by changes in the plasma concentrations of atrial natriuretic factor (ANF), arginine vasopressin (AVP), and/or angiotensin II (ANG II). To explore this, hypertonic NaCl or mannitol was infused intravascularly over 10 min into chronically catheterized fetal sheep and their mothers simultaneously, followed by a 2-h maternal infusion at 1-2 ml/min to maintain the elevated osmolality. Fetal osmolality rose by 16 mosmol/kgH2O during 13% mannitol and 2.5% NaCl infusions and by 57 mosmol/kgH2O during 7% NaCl infusions. Large increases in fetal urine flow occurred in the three groups with peak flows (average of 304%, P less than 10(-6)) at 0-4 min after the end of the infusion. Flow declined to preinfusion values in all groups at 30-40 min. These changes in urine flow occurred in parallel with a rise (to 223%, P less than 10(-6)) and fall in plasma ANF concentrations. One hour after the infusions, urine flow declined to 50% of control concomitant with elevations in plasma AVP (to 414%, P less than 10(-6)), whereas plasma ANG II concentration did not change. Thus the initial increase in fetal urine flow in response to acute hypertonic infusions is temporally related to a rise in fetal plasma ANF, whereas the subsequent fall in urine flow is temporally related to a fall in plasma ANF and a simultaneous rise in AVP concentration. This suggests that ANF may contribute to the acute urine flow increase after hypertonic infusion, whereas AVP appears to be more important for the long-term regulation of fetal urine flow.


1995 ◽  
Vol 268 (5) ◽  
pp. F868-F875 ◽  
Author(s):  
M. E. Wlodek ◽  
R. A. Brace ◽  
M. L. Cock ◽  
S. B. Hooper ◽  
R. Harding

Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure.


1994 ◽  
Vol 267 (6) ◽  
pp. R1522-R1527 ◽  
Author(s):  
J. J. Faber ◽  
D. F. Anderson

Nine bilaterally nephrectomized fetal sheep were infused for 6 days with angiotensin I in sterile water, and five nephrectomized fetal sheep were infused for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD) mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and 423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was of normal appearance, two showed moderate hydrops fetalis, and the remaining fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet-to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal body weight excess of water in the angiotensin I-infused fetuses. Six days of angiotensin I infusion caused a gradual rise in fetal arterial blood pressure from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that the fetal edema was due to the elevation in venous pressure. Plasma concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose, glucose, and lactate in the fetus and the ewe did not identify an osmotically active solute responsible for the transplacental attraction of excess water into the conceptus, and the mechanism that attracted this excess water across the placenta remains unclear.


1998 ◽  
Vol 10 (5) ◽  
pp. 405 ◽  
Author(s):  
Yves Garnier ◽  
Richard Berger ◽  
Doris Pfeiffer ◽  
Arne Jensen

Asphyxia is one of the major causes of perinatal brain damage and neuronal cell loss, which may result in psychomotor deficits during later development. It has been shown previously that the immature brain can be protected from ischemic injury by flunarizine, a class IV calcium antagonist. However, cardiovascular side-effects of flunarizine, when applied at the dosages used in those studies, have been reported. Recently, the present authors were able to demonstrate that even by injecting flunarizine at a far lower dosage (1 mg kg) estimated bodyweight) neuronal cell damage, caused by occlusion of both carotid arteries for 30 min, can be reduced in fetal sheep near term. The aim of the present study was, therefore, to examine whether low-dose flunarizine affects fetal cardiovascular responses to acute asphyxia in sheep near term. Ten fetal sheep were chronically instrumented at a mean gestational age of 132 1 days (term is at 147 days). Fetuses from the study group received a bolus injection of flunarizine (1 mg kg–1 estimated fetal weight) 60 min before asphyxia, whereas the solvent was administered to the fetuses from the control group. Organ blood flows, physiological variables and plasma concentrations of catecholamines were measured before, during and after a single occlusion of uterine blood flow for 2 min (i.e. at 0, 1, 2, 3, 4, and 30 min). Before asphyxia, the distribution of combined ventricular output and physiological variables, as well as concentrations of catecholamines, in fetuses from the control group were in the normal range for chronically prepared fetal sheep near term. During acute asphyxia there was a redistribution of cardiac output towards the central organs accompanied by a pronounced bradycardia and a rapid increase in arterial blood pressure. After asphyxia circulatory centralization did not resolve quite as rapidly as it developed, but was almost completely recovered at 30 min after the insult. There were nearly no differences in the time course of physiological and cardiovascular variables measured before, during and after acute intrauterine asphyxia between the control and study groups. From the present study it was concluded that low-dose flunarizine does not affect short-term fetal circulatory responses to acute asphyxia in sheep near term.


1990 ◽  
Vol 259 (4) ◽  
pp. R745-R752 ◽  
Author(s):  
K. A. Dickson ◽  
S. B. Hooper ◽  
I. C. McMillen ◽  
R. Harding

Our aim was to determine fetal and maternal endocrine and fluid-balance responses to prolonged loss of amniotic and allantoic fluids in sheep. In seven sheep, amniotic and allantoic fluids were drained [379.1 +/- 20.1 (SE) ml/day] from 107 to 135.3 +/- 0.6 days of gestation (term: 145 days). The results from these sheep were compared with those from seven control sheep. Maternal water intake, urine production, and urine osmolality were not altered by fluid drainage, nor were fetal and maternal arterial blood gases, pH, or plasma osmolalities. Fluid drainage increased amniotic, but not allantoic, fluid osmolality. Maternal plasma cortisol concentration increased with fluid drainage, but maternal plasma concentrations of prolactin and arginine vasopressin were unchanged. Fluid drainage increased prolactin concentrations in fetal plasma and amniotic fluid, but fetal plasma concentrations of cortisol (hydrocortisone), arginine vasopressin, norepinephrine, and epinephrine were unchanged. Our results show that the fetus is capable of maintaining its plasma osmolality despite prolonged loss of fluid from its amniotic and allantoic sacs and that this is associated with alterations in the production rate and the composition of amniotic fluid.


2005 ◽  
Vol 288 (5) ◽  
pp. F964-F968 ◽  
Author(s):  
D. Anderson ◽  
Q. Yang ◽  
A. Hohimer ◽  
J. Faber ◽  
G. Giraud ◽  
...  

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).


1995 ◽  
Vol 7 (5) ◽  
pp. 1311 ◽  
Author(s):  
EM Wintour ◽  
R Riquelme ◽  
C Gaete ◽  
C Rabasa ◽  
E Sanhueza ◽  
...  

Samples of maternal and fetal plasma, fetal urine, and amniotic fluid were collected from 8 chronically cannulated pregnant llamas, in the last third of gestation. The samples were obtained for up to 18 days post-surgery. Osmolality, sodium (Na), potassium (K), chloride (Cl), and urea were measured on 40 samples collected on days 1, 2, 3, 4-5, 6-7, 8-9, and 10-19. The osmolalities of maternal and fetal plasma, fetal urine and amniotic fluid, averaged over these 7 time periods, were, respectively, 312 +/- 2, 311 +/- 1, 484 +/- 14, and 317 +/- 1 mosmol kg-1. Values are given as mean +/- s.e. The major differences from fetal fluid values in the ovine fetus (from previously published values) were the higher osmolality and urea concentration of llama fetal urine. Urine flow rate measured in 6 fetuses, 4.5-6.5 kg body weight, was 5.8 +/- 0.4 mliter h-1; urea clearance rate was 55.5 +/- 11.8 mliter h-1. Glomerular filtration rate (GFR), measured with 51Cr-EDTA in 5 fetuses on 1-4 occasions, was 111.4 +/- 23.3 mliter h-1. Fractional reabsorptions (FR) of Na, K and Cl were 97.9 +/- 1, 75.9 +/- 13.5 and 97.7 +/- 0.4% respectively. The GFR (25 mliter kg-1 h-1) and urine flow rate (1 mL kg-1 h-1) were less than half and about one-tenth the respective values in ovine fetuses. As Na reabsorption is the major oxygen-consuming activity of the kidney, the llama fetal kidney requires only half the oxygen needed by the ovine fetal kidney to reabsorb the filtered sodium load. The reason for the formation of hypertonic, rather than hypotonic, urine in the fetal llama may be due to both greater morphological maturity of the kidney and the excretion of as yet unidentified osmotically active organic substances.


1996 ◽  
Vol 81 (6) ◽  
pp. 2588-2594 ◽  
Author(s):  
Stephanie E. Mann ◽  
Mark J. M. Nijland ◽  
Michael G. Ross

Mann, Stephanie E., Mark J. M. Nijland, and Michael G. Ross.Ovine fetal adaptations to chronically reduced urine flow: preservation of amniotic fluid volume. J. Appl. Physiol. 81(6): 2588–2594, 1996.—Adequate amniotic fluid (AF) volume is maintained by a balance of fetal fluid production (lung liquid and urine) and resorption (swallowing and intramembranous flow). Because fetal urine is the principle source of AF, alterations in urine flow and composition directly impact AF dynamics. Intra-amniotic 1-desamino-8-d-arginine vasopressin (DDAVP) is rapidly absorbed into fetal plasma and induces a marked fetal urinary antidiuresis. To examine the effect of intra-amniotic- DDAVP-induced fetal urinary responses on AF volume and composition, six chronically prepared ewes with singleton fetuses (gestation 128 ± 2 days) were studied for 72 h after a single intra-amniotic DDAVP (50-μg) injection. After DDAVP, fetal urine osmolality significantly increased at 2 h (157 ± 13 to 253 ± 21 mosmol/kg) and remained elevated at 72 h (400 ± 13 mosmol/kg). Urinary sodium (33.0 ± 4.5 to 117.2 ± 9.7 meq/l) and chloride (26.0 ± 2.8 to 92.4 ± 8.1 meq/l) concentrations similarly increased. AF osmolality increased (285 ± 3 to 299 ± 4 mosmol/kgH2O), although there was no change in fetal plasma osmolality (294 ± 2 mosmol/kg). Despite a 50% reduction in fetal urine flow (0.12 ± 0.03 to 0.05 ± 0.02 ml ⋅ kg−1 ⋅ min−1at 2 h and 0.06 ± 0.01 ml ⋅ kg−1 ⋅ min−1after 72 h), AF volume did not change (693 ± 226 to 679 ± 214 ml). There were no changes in fetal arterial blood pressures, pH,[Formula: see text], or[Formula: see text] after DDAVP. We conclude the following. 1) Intra-amniotic DDAVP injection induces a prolonged decrease in fetal urine flow and increases in urine and AF osmolalities. 2) Despite decreased urine flow, AF volume does not change. We speculate that, in response to DDAVP-induced fetal oliguria, reversed intramembranous flow (from isotonic fetal plasma to hypertonic AF) preserves AF volume.


1987 ◽  
Vol 63 (4) ◽  
pp. 1463-1468 ◽  
Author(s):  
B. J. Koos ◽  
H. Sameshima ◽  
G. G. Power

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2–3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.


1987 ◽  
Vol 252 (2) ◽  
pp. E279-E282 ◽  
Author(s):  
C. Y. Cheung ◽  
D. M. Gibbs ◽  
R. A. Brace

To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration (13 +/- 2 pg/ml) was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.


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