Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: Effects of a non-peptide antagonist for atrial natriuretic peptide receptor

Gary (Michael) Silberbach, Lori L. Woods, Alan (Roger) Hohimer, Takahiro Shiota, Yuzuru Matsuda, Lowell Davis

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natri-uresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 ± 7 to 234 ± 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 ± 0.7 versus 34.6 ± 2.3% and 0.7 ± 0.1 versus 2.6 ± 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 ± 94 versus 497 ± 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 ± 0.03 to 0.70 ± 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 ± 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 ± 0.13 to 0.25 ± 0.06 and 1.30 ± 0.66 ± 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 ± 5 to 9 ± 2 and 83 ± 16 to 39 ± 5 μj-mol/min). GFR decreased after HS (3.0 ± 0.8 to 2.4 ± 0.5 and 3.6 ± 0.3 to 2.6 ± 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 ± 2.7 to 2.7 ± 0.5 and 16.1 ± 2.4 to 11 ± 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 ± 37 to 436 ± 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Original languageEnglish (US)
Pages (from-to)722-728
Number of pages7
JournalPediatric Research
Volume38
Issue number5
StatePublished - 1995

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Atrial Natriuretic Factor Receptors
Atrial Natriuretic Factor
Anemia
Sheep
Fetus
Sodium
Kidney
Renal Circulation
Urine
Central Venous Pressure
Microcirculation
Hemorrhage
Polyhydramnios
Hydrops Fetalis
Natriuresis
Inulin
Guanylate Cyclase
Diuresis
Nephrons
Extracellular Fluid

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus : Effects of a non-peptide antagonist for atrial natriuretic peptide receptor. / Silberbach, Gary (Michael); Woods, Lori L.; Hohimer, Alan (Roger); Shiota, Takahiro; Matsuda, Yuzuru; Davis, Lowell.

In: Pediatric Research, Vol. 38, No. 5, 1995, p. 722-728.

Research output: Contribution to journalArticle

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abstract = "Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natri-uresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 ± 7 to 234 ± 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 ± 0.7 versus 34.6 ± 2.3{\%} and 0.7 ± 0.1 versus 2.6 ± 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 ± 94 versus 497 ± 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 ± 0.03 to 0.70 ± 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 ± 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37{\%} of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 ± 0.13 to 0.25 ± 0.06 and 1.30 ± 0.66 ± 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 ± 5 to 9 ± 2 and 83 ± 16 to 39 ± 5 μj-mol/min). GFR decreased after HS (3.0 ± 0.8 to 2.4 ± 0.5 and 3.6 ± 0.3 to 2.6 ± 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 ± 2.7 to 2.7 ± 0.5 and 16.1 ± 2.4 to 11 ± 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 ± 37 to 436 ± 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.",
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T1 - Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus

T2 - Effects of a non-peptide antagonist for atrial natriuretic peptide receptor

AU - Silberbach, Gary (Michael)

AU - Woods, Lori L.

AU - Hohimer, Alan (Roger)

AU - Shiota, Takahiro

AU - Matsuda, Yuzuru

AU - Davis, Lowell

PY - 1995

Y1 - 1995

N2 - Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natri-uresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 ± 7 to 234 ± 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 ± 0.7 versus 34.6 ± 2.3% and 0.7 ± 0.1 versus 2.6 ± 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 ± 94 versus 497 ± 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 ± 0.03 to 0.70 ± 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 ± 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 ± 0.13 to 0.25 ± 0.06 and 1.30 ± 0.66 ± 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 ± 5 to 9 ± 2 and 83 ± 16 to 39 ± 5 μj-mol/min). GFR decreased after HS (3.0 ± 0.8 to 2.4 ± 0.5 and 3.6 ± 0.3 to 2.6 ± 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 ± 2.7 to 2.7 ± 0.5 and 16.1 ± 2.4 to 11 ± 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 ± 37 to 436 ± 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

AB - Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natri-uresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 ± 7 to 234 ± 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 ± 0.7 versus 34.6 ± 2.3% and 0.7 ± 0.1 versus 2.6 ± 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 ± 94 versus 497 ± 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 ± 0.03 to 0.70 ± 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 ± 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 ± 0.13 to 0.25 ± 0.06 and 1.30 ± 0.66 ± 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 ± 5 to 9 ± 2 and 83 ± 16 to 39 ± 5 μj-mol/min). GFR decreased after HS (3.0 ± 0.8 to 2.4 ± 0.5 and 3.6 ± 0.3 to 2.6 ± 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 ± 2.7 to 2.7 ± 0.5 and 16.1 ± 2.4 to 11 ± 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 ± 37 to 436 ± 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

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