Vasopressin and neurophysin: high concentrations in monkey hypophyseal portal blood.

Vasopressin and its binding protein, neurophysin, were measured by radioimmunoassay in the hypophyseal portal blood of monkeys after cannulation of individual long portal veins. Mean vasopressin concentrations (13,800 picograms per milliliter) in portal blood were more than 300 times as high as those in the systemic circulation (42 picograms per milliliter). Neurophysin concentration was approximately 25 times as high in portal as in systemic blood. By immunoperoxidase techniques, high concentrations of neurophysin were demonstrated around portal capillaries of the median eminence. These studies indicate direct secretion of vasopressin and neurophysin into the portal circulation; the quantities secreted during stress may be sufficient to exert significant effects on secretion of anterior pituitary hormone.

Cerebrospinal fluid and plasma vasopressin in the fetal lamb: basal concentration and the effect of hypoxia.

The concentrations of vasopressin in the plasma and cerebrospinal fluid (CSF) of the chronically catheterized fetal lamb were measured under basal and hypoxic conditions. Under basal conditions, samples were obtained from 13 fetal lambs of 117-146 days gestation. The mean +/- SEM vasopressin level in CSF was 19.5 +/- 1.5 pg/ml; the mean plasma vasopressin level of 1.9 +/- 0.2 pg/ml was significantly less (P less than 0.001). No consistent change in concentrations of vasopressin in CSF was observed with gestational maturation in 3 animals sampled sequentially or in individual samples obtained over the last 32 days of gestation. The mean vasopressin concentration in the CSF of the pregnant ewe was 5.1 +/- 0.4 pg/ml. The gradients for osmolality, sodium, and potassium between fetal plasma and CSF were: osmolality, 298.4 +/- 1.6 to 304.3 +/- 1.4 mosmol/kg; sodium, 140.9 +/- 0.5-142.5 +/- 0.5 meq/liter; and potassium, 4.3 +/- 0.1 to 3.3 +/- 0.1 meq/liter. Fetal hypoxia was induced by exposure of the ewe to 10% O2 in N2 for 30 min. The concentration of vasopressin increased from 1.7 +/- 0.3 to 277 +/- 144 pg/ml (P less than 0.001) in fetal plasma and from 21.4 +/- 3.8 to 47.1 +/- 9.9 pg/ml (P less than 0.04) in fetal CSF. When the ewe was exposed to room air under comparable experimental conditions, no similar changes in plasma or CSF vasopressin levels were observed in the fetus. Infusion of vasopressin into the fetal jugular vein at 1.0 mU/min for 30 min increased plasma concentrations from 2.3 +/- 0.5 to 83 +/- 17 pg/ml, while the CSF vasopressin values were 31.9 +/- 5.9 (basally) and 30.7 +/- 4.8 pg/ml (after infusion). Mean plasma and CSF osmolality, sodium, and potassium were not changed by any of these experimental interventions. We conclude that 1) under basal conditions, high concentrations of vasopressin are present in the CSF of the fetal lamb, the blood-CSF barrier appears to be impermeable to vasopressin, and concentrations of the hormone in fetal plasma are less than those in CSF; and 2) hypoxia is a potent stimulus of vasopressin release in both fetal plasma and CSF. The route of vasopressin released into the fetal CSF may be distinct from that released into plasma.

Factors in the release of vasopressin by the hypoxic fetus.

The relative effects of 3 stimuli in the release of vasopressin (VP) by the fetus were examined in 19 chronically instrumented fetal lambs, 118-135 days gestational age. The fetus was exposed to: 1) 30-min administration of 10% O2 to the pregnant ewe, 2) 20 min of partial occlusion of the umbilical cord, or 3) 2 min of complete occlusion of the umbilical cord. Twelve studies were conducted for each of these experimental protocols. The rises (mean +/- SE) in plasma VP in the 3 groups were 29.9 +/- 8.9, 48.9 +/- 11.5, and 157.8 +/- 12.5 pg/ml, respectively; the corresponding falls in PaO2 were 9.2 +/- 0.7, 7.7 +/- 0.9, and 12.7 +/- 1.2 mm Hg. pHa did not change in the group receiving 10% O2, fell by 0.11 +/- 0.02 and 0.14 +/- 0.01 after partial and complete occlusion of the umbilical cord. The rises in mean arterial pressure were 6 +/- 2.2, 10 +/- 1.9, and 23 +/- 3.1 mm Hg, respectively, at the end of the 3 procedures. The rise in plasma osmolality ranged from 2-8 mosmol/kg in all 3 groups. Linear regression analyses showed that log VP was negatively correlated with PaO2 (r = -0.827; P less than 0.01) and pHa (r = -0.706; P less than 0.01) and positively correlated to mean arterial pressure (r = 0.607; P = 0.01), but was not significantly correlated to plasma osmolality. Our present findings suggest that hypoxemia and acidemia are associated with and may both be potent stimuli for VP release in the hypoxic fetus. Increased release together with decreased rate of metabolism by the placenta offer an explanation for the very high VP levels found in the neonate after labor and delivery.

Nicotine-stimulated release of neurophysin and vasopressin in humans.

Nicotine stimulation, induced by cigarette smoking, has previously been identified as a potent stimulus for vasopressin release in humans. In this study, radioimmunoassay measurements of plasma vasopressin and human neurophysin were performed on samples taken from 14 normal subjects during cigarette smoking. Significant rises in vasopressin occurred in 10 of the 14 subjects and the same 10 had significant rises in neurophysin. Pretreatment with ethanol in 3 subjects either eliminated or greatly blunted the responses of both vasopressin and neurophysin to cigarette smoking. These studies indicate that the release mechanisms for vasopressin and neurophysin are closely linked in humans.

Volatile (As and Hg) and non-volatile (Pb and Cd) toxic heavy metals analysis in rhizome of Zingiber officinale collected from different locations of North Western Himalayas by Atomic Absorption Spectroscopy.

Ginger is an important ingredient of spice and herbals. The monitoring of toxic heavy metals in the rhizome of ginger is important for protecting public health against the hazards of metal toxicity. The concentration of volatile and non-volatile metals (As, Hg, Pb and Cd), in the soil and rhizome of Zingiber officinale were analyzed using AAS. Soil analysis profile showed uniformity in the metal contents, in active root zone and subsoil, except mercury, which was present in higher quantity in one, out of the four sectors, of the field. The infield metal content in the soil in increasing order was, cadmium < arsenic < lead < mercury. In ginger rhizome the volatile toxic heavy metals arsenic (As) and mercury (Hg) varied from not detected to 0.13 µg/g and 0.01 to 0.42 µg/g, respectively. The non-volatile metals lead (Pb) and cadmium (Cd) ranged from 0.06 to 0.64 µg/g and 0.002 to 0.03 µg/g, respectively(.) The results illustrated the findings that soil is the major but not the only source of metal accumulation in the plants. In our study, the volatile metal content (As, Hg) was found more in rhizomes collected from Himachal Pradesh while the non-volatile metals were predominant in samples from Uttarakhand.

High vasopressin concentrations in human umbilical cord blood--lack of correlation with stress.

Marked elevations in the vasopressin concentrations in human umbilical cord blood have been reported previously (4, 8). This could either be a part of generalized increase in the activity of fetal endocrine system at the time of birth, a phenomenon that has led to the concept of fetal participation in the onset of labor, or simply due to the stress of delivery. The present study is an attempt to examine the later possibility. Plasma vasopressin was determined by radioimmunoassay [9] in separately collected arterial and venous blood from the umbilical cords of 24 babies spontaneously delivered and 14 babies born after Caesarian Section in the absence of labor. Arterial acid-base determinations were done in each case. The Apgar Score was evaluated by one individual. In order to obtain a general idea of circulating concentration of this hormone in the neonatal period, vasopressin concentrations were determined in the systemic venous blood of 12 normal and 10 stressed babies. Vasopressin concentrations in the umbilical arterial blood of babies born after spontaneous delivery were remarkably high, as compared to all the other groups. Despite a wide range, between 5-2200 pg/ml, there was no correlation between the magnitude of vasopressin elevation and the severity of fetal asphyxia (Fig. 1). The present finding in part, confirms and expands previously observed increased vasopressin levels in the cord blood after spontaneous vaginal delivery. In addition, a lack of correlation between fetal asphyxia and the vasopressin levels suggests that these high levels may not be related to this form of stress.

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 micrograms X kg-1 X min-1). During hypotension, renin activity increased from 1.39 +/- 0.49 to 3.92 +/- 1.38 ng X 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.

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.

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

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 less than 0.001) to 200 +/- 59 pg . ml-1 with a delayed increase in amniotic fluid concentrations (P less than 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 less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. After intraamniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion of vasopressin in the hypoxic lamb: comparison between fetus and newborn.

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-day-old). 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 X kg) in the fetus and from 0.15 +/- 0.033 to 0.09 +/- 0.022 ml/(min X 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P less than 0.001) to 200 +/- 59 pg ml-1 with a delayed increase in amniotic fluid concentrations (P less than 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 less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. Following intra-amniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Plasma vasopressin, renin, and catecholamines during nitroprusside-induced maternal and fetal hypotension in sheep.

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).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal response of fetal lamb to complete occlusion of umbilical cord.

The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure.

Role of vasopressin in fetal homeostasis.

The role of vasopressin (VP) and the kidney in the maintenance of solute and volume homeostasis was studied in chronically instrumented fetal lambs during the third trimester. Plasma VP, urine and plasma osmolality, and urine output were measured in 74 simultaneous samples. The results show a strong positive nonlinear correlation between plasma VP and osmolality when a latter is higher than 290 mosmol/kg (r = 0.803, P = 0.03) and between plasma VP and urine osmolality (r = 0.806, P = 0.05). No correlation was found between fetal and maternal plasma VP. However, linear correlations were found in plasma osmolality and sodium concentrations between mother and fetus; mean maternal-fetal gradients were 4 mosmol/kg and 3.1 meq/liter, respectively. The highest values for plasma VP and osmolality found in our study were 7.0 pg/ml and 317 mosmol/kg, respectively. There values corresponded to urine output of 0.02 ml.kg-1.min-1 and osmolality of 517 mosmol/kg. In conclusion, there studies demonstrate that the relationship among plasma osmolality, plasma vasopressin concentration, and urine osmolality in the lamb fetus are qualitatively similar to those of the adult. The results suggest that the fetal neurohypophysis and kidney may participate in the maintenance of fetal osmolar and volume homeostasis.

Vasopressin secretion induced by hypoxia in sheep: developmental changes and relationship to beta-endorphin release.

To investigate the developmental changes in the secretion of vasopressin and the potential role of beta-endorphin as a stimulus to the release of vasopressin, the concentrations of these peptides were measured in fetal, newborn, and adult sheep after episodes of induced hypoxia. The studies confirm that hypoxia is a potent stimulus to the release of both vasopressin and beta-endorphin in the fetal animal. In both the newborn lamb and the ewe, more profound hypoxia is necessary for a similar release. In the fetus, the release of both vasopressin and beta-endorphin after hypoxia increased with gestational maturation. A comparison of control concentrations of both peptides, the discordance of release in the newborn lamb, and the absence of a change in concentrations of vasopressin with infusion of beta-endorphin implies that these hormones are released in parallel but independently during hypoxic stress.

Release of vasopressin by the fetal lamb during premature parturition induced with corticotropin.

These studies were implemented to assess the relationship between fetal vasopressin secretion and the progression of parturition as well as the contribution of specific stimuli to vasopressin release during labor. In chronically catheterized fetal lamb preparations, labor was induced by infusion of adrenocorticotropin (12.5 mg/kg/hr) to seven fetuses at 130 +/- 1 day of gestation. Before labor, fetal plasma vasopressin concentrations were 2.1 +/- 1.4 pg/ml and remained low (5.3 +/- 3.4 pg/ml) during prodromal and early phases of labor, but rose significantly in the active and expulsive phases (39.6 +/- 27.5 and 173.3 +/- 152.9 pg/ml) to reach peak values at delivery (584.2 +/- 433 pg/ml) and decrease by 30 min after birth (359.8 +/- 90.0 pg/ml). At delivery, fetal plasma vasopressin concentrations were strongly correlated (P less than 0.001) with hormone values obtained during the latter phases of labor. Fetal arterial pH and oxygen tension was inversely correlated with plasma vasopressin (P less than 0.01). No similar correlations were found with arterial PCO2, K, Na, Cl, osmolality, or packed cell volume. Unexpectedly, we observed a significant (P less than 0.001) and progressive decrease in fetal oxygen tension during the induction process. Other characteristics of adrenocorticotropin-induced parturition seemed to mimic those of spontaneous labor.