Alan B. Zubrow

Plasma Renin, Catecholamine, and Vasopressin during Nitroprusside-induced Hypotension in Ewes

The effect of acute nitroprusside-induced hypotension on plasma renin activity, catecholamine, and vasopressin concentrations was examined in eight chronically catheterized, conscious ewes. Nitroprusside was infused intravenously for one hour at rates adjusted to achieve a 20% decrease in mean blood pressure (dose range: 14–50 mg, or about 5.8–18.5 μg·kg-1·min-1). During hypotension, renin activity increased from 1.39 ± 0.49 to 3.92 ± 1.38 ng·ml-1.·h-1, catecholamine concentrations remained unchanged, and vasopressin increased from 1.7 ± 0.4 to 110 ± 52.7 pg/ml. A significant positive correlation was obtained between total nitroprusside dose and peak vasopressin level (r=0.749, P =0.015). No significant change in arterial-blood (PH, PO2, PCO2, plasma osmolality, or sodium concentration were observed throughout the experiment, thus eliminating the possibility of osmolar or hypoxic stimuli for the increased renin activity and vasopressin release. The magnitude of vasopressin release found in our studies implies that it plays a more important role than renin in defense against acute hypotension. In addition, the authors experiments suggest that variation in vasopressin release may be responsible for the variation of the dose of nitroprusside required to maintain hypotension.

Vasopressin concentration in amniotic fluid as an index of fetal hypoxia: mechanism of release in sheep.

Summary: Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep and, in turn, plasma concentrations of the hormone correlate inversely with fetal oxygenation. Because 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. We therefore 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 111–141 d 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. After exposure of the ewe to 10% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P < 0.001) to 200 ± 59 pg.ml-1 with 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. After intraamniotic injection of vasopressin, levels remained increased for at least 24 h.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 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 intra-uterine pressure were discerned.

Effects of hypoxia on vasopressin concentrations in cerebrospinal fluid and plasma of sheep

The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less than 0.001) higher than the concentration in arterial plasma (2.4 +/- 0.2 pg/ml). There was a significant positive correlation between CSF and plasma vasopressin concentrations (r = 0.66, p less than 0.01). The introduction of severe hypoxia by exposure of the sheep to an inspired gas mixture of 5% O2 in N2, a known stimulus to systemic release of vasopressin, was associated with an increase in the concentration of vasopressin in plasma to 339 +/- 65 pg/ml and CSF to 19 +/- 3.9 pg/ml. This increase of vasopressin in CSF was delayed in time with respect to the increases in the plasma and of a lesser magnitude. With moderate hypoxia (10% O2 in N2 exposure) no increase in CSF or plasma vasopressin concentration was observed, suggesting a threshold response. Intravenous infusion of vasopressin to achieve plasma values comparable to those seen with hypoxia was not accompanied by a significant increase in CSF vasopressin concentration. Thus, severe hypoxia is a potent stimulus for release of vasopressin into both CSF and plasma. Furthermore, data suggest that vasopressin may be released into CSF via a separate route from that released into plasma.

Plasma Vasopressin, Renin, and Catecholamines during Nitroprusside-Induced Maternal and Fetal Hypotension in Sheep

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-1 to 208 ±153 pg · ml-1 and plasma renin activity increased from 1.5 ± 0.3 ng · ml-1 · h-1 to 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-1 and 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-1 to 1054 ± 772 pg · ml-1, plasma renin activity increased from 5.7 ± 2.2 ng · ml-1 to 22.2 ± 7.1 ng · ml-1 · h-1, and total catecholamines from 174 ± 58 pg · ml-1 to 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.

Plasma vasopressin, renin and catecholamines during nitroprusside-induced hypotension in the newborn lamb.

The circulating levels of vasopressin, catecholamines and renin activity before, during and following a 10-20% fall in mean arterial blood pressure induced by sodium nitroprusside were measured in six chronically catheterized lambs during the first week of life. No significant changes in pHa, PaO2, PaCO2, Plasma sodium or osmolality were observed during or following the infusion of sodium nitroprusside at an average of 12 g.kg-1.min-1 (table I). However, the fall in blood pressure at the end of 60 minutes infusion, was associated with significant increases in the plasma levels of vasopressin from a control value of 2.4 +/- 0.57 to a maximum of 35.1 +/- 16.3 pg/ml (p = .002), renin activity from 6.7 +/- 1.56 to 27.4 +/- 11.44 ng.ml-1.hr-1 (p = .003), and catecholamines from 189.3 +/- 42.15 to 543.3 +/- 100.52 pg.ml-1 (p = .0001). The increase in vasopressin is lower, while that of PRA was higher and catecholamines similar to those found in the ewe. Plasma renin activity (PRA) and catecholamine levels remained elevated for at least 30 minutes following the end of the infusion while the mean blood pressure rose significantly above control levels and remained elevated for twenty minutes. We speculate that the persistent elevated levels of vasoactive mediators are responsible for the prolonged rebound hypertension following the cessation of the nitroprusside infusion and is the result of an immaturity of either a feedback process or metabolism of the vasoactive mediators or a combination of both mechanisms. This rebound hypertension could have adverse effects particularly in the very immature neonate.

1567 RESPONSE OF THE NEWBORN TO INDUCED HYPOTENSION

The response of vasoactive mediators in the neonate to a 20% fall in mean arterial blood pressure (MBP) was studied in six chronically catheterized lambs 4-7 days old, following infusion of sodium nitroprusside (SNP). No significant change in pHa, PaCO2, plasma sodium or osmolality was observed following the infusion of SNP. However, the fall in MBP from 65.3±3.90 to 53.8±2.82 mmHg (Mean ±S.E.) at the end of sixty minutes infusion was associated with the following changes in vasopressin (VP), renin activity (PRA) and catecholamine concentrations (CA) (*p<0.01):These levels remained significantly elevated for at least thirty minutes after the end of infusion while MBP rose above control values and was still elevated (72.8±2.95 mmHg) after sixty minutes. These experiments demonstrate that as in the adult, the newborn sheep responds promptly to a hypotensive episode by secreting vasoactive mediators which may play an important role in blood pressure homeostasis. The prolonged hypertension that followed suggests that as in the fetus, blood pressure is not well regulated due to either slower metabolism or immaturity of feedback mechanisms controlling the release of vasoactive mediators.

RESPONSE OF FETAL VASOACTIVE MEDIATORS TO INDUCED HYPOTENSION

To characterize the fetal response to change in blood pressure vasoactive mediators were measured during and after 60 min of sodium nitroprusside induced hypotension. Fetal arterial blood pressure was lowered by 10-20% in seven chronically catheterized fetal lambs (116-135 d). Fetal pHa (7.39±0.01), paCO2 (40.7±1.1 torr), PaO2 (22.1±0.9 torr), Osm (297.3±3 mosm/kg), and Na (144.5±1.4 meq/1 remained unchanged. Results (mean ±SEM, analyzed using ANOVA) on log plasma vasopressin (V), renin activity (PRA), epinephrine (E) and norepinephrine (NE) were:These experiments demonstrate that the fetus responds promptly to a hypotensive stress by secreting vasoactive mediators. We speculate that vasopressin and renin play an important role in the maintenance of fetal blood pressure, catecholamines playing a secondary role.

399 FACTORS IN THE RELEASE OF VASOPRESSIN BY THE FETUS DURING HYPOXIC STRESS

The contribution of various factors to the release and high level of vasopressin(VP)by the fetus during hypoxic stress were examined in 27 chronically instrumented fetal lambs,118 to 135 days gestational age. They were exposed to: a)30 minutes administration of 10% O2 to the pregnant ewe (H):b) 20 minutes partial occlusion of the umbilical cord(POC); or,c) 2minutes complete occlusion of the umbilical cord(COC). The change in fetal arterial blood pressure and plasma composition were:These results indicate that osmolality is probably not a major factor in the release of VP under hypoxic stress. While hypoxemia alone does stimulate VP release, the higher VP levels following POC compared to H indicate that other factors leading to acidemia may also contribute. The rapid rise of plasma VP following 2 min. of COC during which the placental bed is temporarily excluded from the fetal circulation suggests that the placenta plays an important role in metabolism of the hormone. The large increase in BP could also be important in stimulating release of the hormone.

1475 INCIDENCE OF TACHYPNEA FOLLOWING MECONIUM ASPIRATION

Eighty-two consecutive infants born through meconium stained amniotic fluid were prospectively followed to determine the incidence of tachypnea (respiratory rate greater than 50 during a 24 hour period) at the time of discharge. These infants represented 8.3% of all deliveries during the study period. Eighty-five percent were intubated in the delivery room; 39% had meconium aspirated from below the vocal cords. All infants received percussion and suctioning after birth. Seventy percent of the infants were born vaginally and 30% by caesarean section. The study population had a mean birth weight of 3420 grams, gestational age of 40.1 weeks, 1 minute Apgar of 6, 5 minute Apgar of 8. Respiratory rates were recorded every four hours until discharge or until normal for 24 hours.Twenty infants (24%) were still tachypneic at discharge; 16 were born vaginally and 4 by caesarean section. Nonparametric correlation coefficient and multivariable discriminate analysis revealed no predictability of the recorded variables (route of delivery, 1 minute Apgar, 5 minute Apgar, birth weight, gestational age, presence of meconium below the vocal cords) with tachypnea. Tachypnea at discharge following meconium aspiration has not been previously described. The pathophysiology of tachypnea in these infants requires further study.