Atrial natriuretic factor in maternal and fetal sheep

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.

1995 ◽  
Vol 268 (6) ◽  
pp. R1411-R1417
Author(s):  
D. Javeshghani ◽  
S. Mukaddam-Daher ◽  
L. Fan ◽  
Z. Guan ◽  
J. Gutkowska ◽  
...  

Previous studies of the atrial stretch-atrial natriuretic factor (ANF) relationship during pregnancy have employed volume expansion and measured only right atrial pressure (RAP). Consequently, we studied nonpregnant (n = 7) and 115- to 125-day pregnant (n = 7) sheep and assessed the ANF response to changes of RAP and left atrial pressure (LAP) induced by graded balloon inflation. Ewes prepared with vascular catheters and atrial balloons were studied after recovery from preparatory surgical procedures. The basal levels of mean arterial pressure (MAP, 83 +/- 3 mmHg), RAP (2.1 +/- 0.7 mmHg), LAP (4.7 +/- 0.9 mmHg), and heart rate (HR, 102 +/- 6 beats/min) were similar in nonpregnant and pregnant sheep. Pregnancy also resulted in elevation of ANF concentration from 25 +/- 6 to 57 +/- 4 fmol/ml. With right atrial distension, the RAP-ANF relationships were similar in both nonpregnant and pregnant sheep, with a 10-mmHg increase in RAP increasing ANF by an average of 95 +/- 9 fmol/ml. In nonpregnant sheep, the LAP-ANF relationship was more responsive than RAP-ANF because a 10-mmHg increase in LAP resulted in a 193 +/- 10 fmol/ml increase in ANF. Moreover, during pregnancy, the LAP-ANF relationship was significantly more sensitive because a 10-mmHg increase in LAP resulted in a 433 +/- 15 fmol/ml elevation of ANF. These data demonstrate that plasma ANF levels are more responsive to distension of the left atria than to the right. More importantly, the ANF response to left, but not right, atrial distension is enhanced by pregnancy.


1989 ◽  
Vol 257 (3) ◽  
pp. R580-R587 ◽  
Author(s):  
R. A. Brace ◽  
L. A. Bayer ◽  
C. Y. Cheung

The purpose of this study was to determine the effects of atrial natriuretic factor (ANF) in the fetus and to explore the interactions among the fetal cardiovascular, endocrine, and fluid responses to ANF. In 12 chronically catheterized fetal sheep at 130 +/- 1 (SE) days gestation, ANF was infused intravenously for 30 min at 14-300 ng.min-1.kg-1. Fetal arterial plasma ANF concentration increased by 174 to 5,410 pg/ml from a preinfusion value of 163 +/- 13 pg/ml. The clearance of ANF from the circulation was 122 +/- 28 ml.min-1.kg-1 and the half-life was 0.46 +/- 0.07 min. When plasma ANF was greater than 2,000 pg/ml, fetal arterial pressure decreased, venous pressure increased transiently, and heart rate was unchanged. Plasma arginine vasopressin (AVP) concentration and plasma renin activity (PRA) increased with high ANF concentrations, while norepinephrine concentrations were unaffected. Fetal blood volume decreased in all fetuses, and urine flow increased significantly but not in every fetus. Blood and urine osmolalities did not change. On terminating the infusion, venous pressure and urine flow decreased below control, while blood volume and arterial pressure remained reduced. Plasma AVP concentration increased further, and this was accompanied by an increase in urine osmolality. Thus the most consistent effect of ANF in the fetus was a reduction in blood volume, which was independent of urine flow changes. Other cardiovascular, endocrine, and fluid responses to ANF as well as interactions among them appeared to occur largely at supraphysiological concentrations and may be secondary to the changes in blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 ◽  
Vol 257 (4) ◽  
pp. E466-E472 ◽  
Author(s):  
C. Y. Cheung ◽  
L. K. Miner ◽  
R. A. Brace

This study was designed to explore the effect of hyperosmolality on fetal plasma atrial natriuretic factor (ANF) concentrations in chronically catheterized sheep fetuses averaging 133 days gestation. An isotonic solution of 0.9% NaCl or hypertonic solution of 2.5% NaCl, 13% mannitol, or 7% NaCl was infused intravascularly into the fetuses at 20 ml/kg over 10 min and simultaneously into their mothers. Fetal plasma osmolality changed by -2 +/- 1 (SE) mosmol/kg in the isotonic group and by 16 +/- 2, 20 +/- 4, and 56 +/- 3 mosmol/kg in the 2.5% NaCl, 13% mannitol, and 7% NaCl groups, respectively (P less than 0.00001). Preinfusion fetal ANF levels were similar in all four groups and averaged 145 +/- 7 (SE) pg/ml. With infusion, fetal plasma ANF increased significantly in the isotonic group by 28 +/- 6%. In the 2.5% NaCl and 13% mannitol groups, the increment in plasma ANF was four times, whereas in the 7% NaCl group it was eight times that in the isotonic group (P less than 0.01). Blood volume and venous pressure changes were similar in all groups. In the hypertonic groups, plasma ANF and venous pressure returned to control levels within 1 h after the start of the infusion, whereas plasma osmolalities remained elevated. Thus infusions of hypertonic solutions into the ovine fetus caused much greater increases in plasma ANF concentrations compared with those seen with isotonic infusion. The return of plasma ANF levels to control despite maintained hyperosmolality suggests that hyperosmolality stimulated ANF release either by a direct but transient mechanism or by potentiating the effects of vascular volume expansion.


1988 ◽  
Vol 254 (1) ◽  
pp. R40-R46
Author(s):  
M. G. Ervin ◽  
M. G. Ross ◽  
R. Castro ◽  
D. Sherman ◽  
R. W. Lam ◽  
...  

Studies were conducted to quantify ovine fetal and adult atrial natriuretic factor (ANF) metabolism. A total of 14 pregnant ewes with singleton fetuses were prepared with vascular catheters. In protocol 1, six fetuses (mean gestation, 131 +/- 1 days) received intravenous infusions of synthetic human ANF (hANF, 100 ng.min-1.kg-1) for 60 min. Mean basal fetal plasma ANF levels increased from 180 +/- 44 pg/ml to a steady-state level of 1,233 +/- 192 pg/ml. In protocol 2, five fetuses (mean gestation, 130 +/- 1 days) received successive 40-min infusions of hANF at 5, 25, and 100 ng.min-1.kg-1. Although basal fetal plasma ANF levels (522 +/- 135 pg/ml) were greater than those observed in protocol 1, fetal plasma ANF levels increased to 1,580 +/- 295 pg/ml at the highest infusion rate. In both protocols 1 and 2, basal fetal plasma ANF levels were three- to fourfold greater than maternal levels. The fetal plasma ANF clearance rates calculated from protocol 1 and from the 25- and 100-ng.min-1.kg-1 infusions from protocol 2 were similar (89 +/- 10, 120 +/- 31, and 116 +/- 38 ml.min-1.kg-1, respectively) and were combined to yield a mean estimated fetal plasma ANF clearance rate of 102 +/- 11 ml.min-1.kg-1. In protocol 3, adult plasma ANF levels increased from 137 +/- 36 to 4,142 +/- 776 pg/ml in response to ANF infusion at 200 ng.min-1.kg-1. The mean plasma ANF clearance rate calculated for the adult animals was 59 +/- 12 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)


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.


1991 ◽  
Vol 165 (6) ◽  
pp. 1635-1641 ◽  
Author(s):  
Michael G. Ross ◽  
John P. Cardin ◽  
Lony Castro ◽  
M. Gore Ervin ◽  
Rosemary D. Leake

1994 ◽  
Vol 267 (5) ◽  
pp. R1413-R1420
Author(s):  
S. Mukaddam-Daher ◽  
J. Gutkowska ◽  
B. S. Nuwayhid ◽  
E. W. Quillen

Plasma atrial natriuretic factor (ANF) is normally released into the circulation primarily by volume expansion and atrial distension, but we have shown that plasma ANF is elevated in pregnant sheep before volume expansion. Because alterations in the metabolic clearance of ANF could lead to elevated plasma ANF levels, the present study was designed to determine the pharmacokinetics of plasma ANF in pregnant sheep. Chronically instrumented nonpregnant and pregnant sheep received intravenous injections of monoiodinated human ANF (125I-hANF). Plasma decay curves of 125I-hANF followed a biexponential function in both groups. High-performance liquid chromatography (HPLC) revealed the accumulation of smaller degradation products by 2 min postinjection, and by 30 min no intact ANF was present. Because HPLC identification of ANF and its metabolites was shown to be more efficient than precipitation with 10% trichloroacetic acid (TCA) or extraction by Sep-Pak cartridges, ANF kinetic parameters were calculated from HPLC-corrected plasma decay curves. Injected ANF was rapidly distributed in an initial distribution volume (IDV) that was expanded in pregnant sheep. Metabolic clearance rate (MCR) was greater in pregnant sheep (2.8 +/- 0.3 vs. 6.8 +/- 1.2 l/min, P = 0.002), while plasma half-life (t1/2) was not altered (2.2 +/- 0.5 vs. 2.4 +/- 0.4 min). The data demonstrate that during pregnancy, the t1/2 of ANF is not altered but the MCR of ANF is enhanced. These findings imply that plasma ANF is increased by mechanisms other than reduced clearance in pregnant sheep.


1992 ◽  
Vol 263 (4) ◽  
pp. F671-F679 ◽  
Author(s):  
M. E. Wlodek ◽  
R. Harding ◽  
G. D. Thorburn

Our aim was to determine the effects of prolonged removal of fetal urine during late gestation on fetal-maternal fluid and electrolyte relationships. We measured the volume and composition of fetal urine and amniotic and allantoic fluids and the composition of fetal and maternal plasma in sheep before and during continuous urine drainage, which began at 130 days of gestation and continued until the onset of labor; a control group was also studied. The response to fetal urine drainage occurred in two phases. In the "acute" phase (1-3 days), amniotic and allantoic fluid volumes decreased significantly, presumably due to their reabsorption into the fetal chorionic circulation or swallowing of amniotic fluid by the fetus. During the "chronic" phase, starting 3-5 days after urine drainage, a significant reversal in the transplacental osmotic gradient occurred due to a decrease in maternal plasma osmolality. During the entire drainage period (14.1 +/- 1.1 days, mean +/- SE, n = 5) at least 542 ml/day of water and 24 mmol/day of electrolytes passed from the mother into the fetal circulation and fetal plasma osmolality was unchanged. We conclude that, despite the loss of substantial water and electrolytes, the fetus is able to maintain its growth and fluid and electrolyte homeostasis by obtaining water and electrolytes initially from the amniotic and allantoic fluids and subsequently from its mother. The movement of water and electrolytes to the fetus would have been facilitated by the reversed transplacental osmotic gradient.


1996 ◽  
Vol 270 (5) ◽  
pp. R1132-R1140
Author(s):  
L. Fan ◽  
S. Mukaddam-Daher ◽  
J. Gutkowska ◽  
B. S. Nuwayhid ◽  
E. W. Quillen

Volume-loading and intravenous infusion studies have suggested that the natriuretic response of atrial natriuretic factor (ANF) is blunted or unaltered during pregnancy, but these findings may be influenced by changes in peripheral metabolism or clearance. To better define the direct renal actions of ANF, three doses (0.3, 1.5, and 3.0 pmol.kg-1.min-1) of ANF were infused directly into the renal artery of nonpregnant (n = 7) and 115- to 135-day pregnant (n = 6) unilaterally nephrectomized conscious sheep. Each dose was administered on a separate day according to a protocol that consisted of two 20-min control periods, two 20-min ANF infusions, and three 30-min recovery periods. The levels of basal mean arterial pressure averaged 86 +/- 25 mmHg and were similar and constant throughout all protocols in nonpregnant and pregnant ewes. Glomerular filtration rate (GFR) and renal blood flow (RBF) were increased during pregnancy, but GFR, RBF, and fractional proximal tubular reabsorption were not significantly altered by infusion of ANF. Nonpregnant sheep exhibited a selective renal response that was limited to an increase in urinary sodium excretion (UNaV). Pregnant sheep exhibited a selective renal response that included increases in UNaV and urine flow rate produced by suppression of distal sodium and, presumably, fluid reabsorption. The natriuretic and diuretic response of pregnant sheep was much greater than that of nonpregnant sheep despite a smaller proportional increment in intrarenal ANF concentration. These data suggest that the ovine renal response to ANF is limited to actions on the distal tubule that are enhanced during pregnancy.


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