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Summary: Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep, and plasma concentrations of the hormone correlate inversely with fetal oxygenation. Since the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. Therefore, we measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs between 111 and 141 days gestation. In the resting state, mean (±SE) vasopressin concentrations in amniotic fluid (1.6 ± 0.3 pg ml-1) did not differ from those in maternal (1.4 ± 0.4 pg ml-1) or fetal (1.8 ± 0.2 pg ml-1) plasma. Following exposure of the ewe to 10% O2or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P < 0.001) to 200 ± 59 pg ml-1with a delayed increase in amniotic fluid concentrations (P < 0.03) to 15.8 ± 4.5 pg ml-1. This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r =0.83; P < 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P < 0.02) and sustained increase of vasopressin in amniotic fluid. Following intra-amniotic injection of vasopressin, levels remained increased for at least 24 h.Thus, in the third trimester of ovine gestation, amniotic fluid vasopressin concentration was a reliable indicator of prior fetal hypoxia. Parallel amounts of antidiuretic activity measured by bioassay and vasopressin measured by radioimmunoassay confirmed the presence of active hormone in amniotic fluid. Hypoxia alone was not a stimulus to passage of meconium, and increased concentrations of vasopressin in fetal plasma were not associated with expulsion of meconium in utero. Despite elevated concentrations of vasopressin in amniotic fluid, no associated changes in intrauterine pressure were discerned.

ABSTRACT: The release of vasopressin, renin, and catecholamines by the fetus during either maternal or fetal hypotension was examined in chronically catheterized fetal lambs. Nitroprusside was infused intravenously for 1 h into seven pregnant ewes (maternal hypotension) or nine fetal lambs (fetal hypotension); the rates were adjusted to achieve a 15 to 30% decrease in mean blood pressure. During maternal hypotension, mean ± SE vasopressin in maternal plasma increased from 1.2 ± 0.2 pg · ml-1to 208 ±153 pg · ml-1and plasma renin activity increased from 1.5 ± 0.3 ng · ml-1· h-1to 6.6 ± 1.6 ng · ml-1· h-1. Fetal vasopressin and plasma renin activity also increased during the same interval from 1.1 ± 0.3 to 16.9 ± 7.5 pg · ml-1and 3.7 ± 1.1 to 10.5 ± 2.85 ng · ml-1· h-1, respectively; but no changes were observed in fetal blood pressure, heart rate, or acid base status. During fetal hypotension, mean vasopressin in fetal plasma increased from 4.3 ± 3.4 pg · ml-1to 1054 ± 772 pg · ml-1, plasma renin activity increased from 5.7 ± 2.2 ng · ml-1to 22.2 ± 7.1 ng · ml-1· h-1, and total catecholamines from 174 ± 58 pg · ml-1to 810 ± 416 pg · ml-1. There was no change in fetal heart rate, acid base status, osmolality, or sodium concentration. The fetus became and remained hypertensive for at least 1 h after the end of infusion. This prolonged hypertension was associated with elevated levels of vasopressin and plasma renin activity. Peak vasopressin levels were proportional to the total nitroprusside dose in both the ewe and fetus (maternal r = 0.796, fetus r = 0.870). These experiments indicate that as in the adult, vasopressin and the renin-angiotensin system in the fetus are stimulated by euvolemic hypotension and may play an important role in the maintenance of fetal blood pressure during an hypotensive challenge. We speculate that the prolonged rebound hypertension represents immaturity of the fetus to fine tune the regulation, release, or metabolism of vasoactive mediators. More likely, the hypertension and elevated hormone levels represent homeostatic mechanisms to combat the nitro-prusside-induced diminished cardiac output. Lastly, fetal release of vasopressin, renin-angiotensin, and norepinephrine during maternal hypotension suggests that they are sensitive indicators of early fetal compromise.

Summary: The factors associated with increased renal excretion of vasopressin (VP) were examined in the hypoxic fetus and newborn. Studies were conducted on six chronically instrumented fetal (117-136 days gestation) and seven newborn lambs (2-6-dayold). Hypoxia was produced by administration of 10% oxygen to the ewe or neonate for 30 min. This procedure caused a 50% reduction in PaO2, no significant change in pHa in either fetus or neonate and a slight fall in PaCO2. Hypoxia caused an increase in VP concentrations in plasma from 1.3 ± 0.53 to 46.4 ± 4.71 pg/ml in the fetus and from 5.9 ± 2.80 to 50.2 ± 26.68 pg/ml in the neonate. After hypoxia there was a fall in urine output from 0.27 ± 0.045 to 0.17 ± 0.046 ml/(min·kg) in the fetus and from 0.15 ± 0.033 to 0.09 ± 0.022 ml/(min·kg) in the newborn. The corresponding values for urine osmolality were the following: 168 ± 30.8 to 325 ± 30.6 mOsm/kg in the fetus and 388 ± 65.4 to 523 ±51.8 mOsm/kg in the newborn. VP concentration in urine increased from 13 ± 9.4 to a maximum of 176 ± 32.4 pg/ml after 30 min of recovery in the fetus and 39 ± 4.6 to 278 ± 132.5 pg/ml after 1 h of recovery in the newborn. These levels remained high for at least 1 h after the end of hypoxia. There was a good linear correlation between plasma VP levels and the corresponding urine levels and excretion rates in both the fetus and newborn. No correlation was found between VP urinary excretion and either osmolar excretion or GFR. These results, therefore, indicate that urinary VP levels and excretion rates can be used as a reflection of levels in plasma after hypoxia.