Hendrik Stegner

Does DDAVP (1-Desamino-8-D-Arginine-Vasopressin) Cross the Blood-CSF Barrier?

Plasma and CSF 1-desamino-8-D-arginine-vasopressin (DDAVP) levels were measured by radioimmunoassay following the infusion at constant rates of various amounts of DDAVP (12.5-20 ng/kg/min) into the jugular veins of 4 adult sheep prepared with chronic, indwelling cisterna magnum catheters, as well as jugular vein and carotid artery catheters. The mean steady-state CSF DDAVP concentration did not vary significantly from zero. Thus, DDAVP does not cross the blood-CSF barrier when administered intravenously.

The Effect of Hypoxia on Neurohypophyseal Hormone Release in Fetal and Maternal Sheep

Summary: The effect of hypoxemia on arginine vasopressin (AVP) and oxytocin (OT) release was investigated in the chronically catheterized fetus and ewe. During 30 min of 10% maternal oxygen delivery, mean (±SEM) arterial Po2 decreased from 105 ± 10.6 to 48 ± 3.5 mm Hg in the ewe and from 21 ± 1.3 to 12 ± 0.8 mm Hg in the fetus (each P < 0.001). Arterial Pco2 decreased from 35 ± 44 to 29 ± 1.0 mm Hg in the ewe, whereas fetal Pco2 decreased from 43 ± 2.3 to 35 ± 3.5 mm Hg (P < 0.05). Blood pH increased from 7.44 ± 0.03 to 7.56 ± 0.04 in the ewe (P < 0.01) and from 7.36 ± 0.004 to 7.40 ± 0.006 in the fetuses (P < 0.01).Baseline mean AVP levels were identical in ewes and fetuses (0.7 ± 0.1 µ μ U/ml). After 30 min of hypoxia, plasma AVP levels remained unchanged in the ewes (0.9 ± 0.1), but increased dramatically in the fetuses (47 ± 21 µ μU/ml) (P < 0.001). There was a highly significant correlation between the duration of hypoxia and log fetal AVP concentrations (r=0.85). The log fetal plasma AVP also was inversely correlated to the log fetal Po2 values (=0.83).Mean baseline fetal and maternal plasma OT levels were 2.6 ± 0.5 µ μU/ml and 2.2 ± 0.5 µ μU/ml, respectively. After 30 min of hypoxia fetal and maternal OT values were 2.9 ± 0.8 µ μU/ml (not significant).

Arginine Vasopressin and Arginine Vasotocin Inhibit Ovine Fetal/Maternal Water Transfer

Summary: After the infusion of 500 ml 20% mannitol to 12 pregnant ewes, we studied maternal and fetal plasma osmolality and maternal hematocrit responses and monitored blood pressure, heart rate, blood gas, and pH in chronically catheterized fetal lambs at 129–140 days gestation. To examine the effect of arginine vasotocin (AVT) and arginine vasopressin (AVP) on fetal/maternal water transfer, the mannitol infusion was repeated 1 day before or after the baseline mannitol study during a 2-h fetal infusion of AVT (7 μU · kg−1 · min−1) or AVP (20–400 μU · kg−1 · min−1) in eight and five animals, respectively. Mannitol was administered to the ewe after 1 h of the 2-h AVT or AVP infusion. The fetal and maternal osmolality and hematocrit responses were compared to the baseline mannitol responses in the same sheep. Maternal and fetal blood gases and pH were measured throughout the study periods during the AVT studies. In four of the ewes, an identical (sham) study was performed substituting 500 ml normal saline for the mannitol infusion to the ewe.Fetal AVP infusion alone produced a significant decrease in fetal plasma osmolality (P < 0.001; two-way analysis of variance) and a slight increase in maternal osmolality (P < 0.05). Fetal AVP or AVT infusion significantly obtunded the fetal osmolality increment induced by maternal mannitol (each P < 0.001); moreover, there was a greater decrease in maternal hematocrit after mannitol alone than after mannitol with AVT (P < 0.05). Fetal hematocrit was maintained unchanged by transfusion with heparinized maternal blood. Maternal and fetal heart rates and maternal blood pressure remained unchanged during the studies. But during the fetal AVT infusion, fetal blood pressure increased from 64 ± 3 to 75 ± 2 mniHg (P < 0.01); fetal and maternal Po2 and pH remain unchanged; and fetal Pco2 increased from 30 ± 2 to 37 ± 4 (P < 0.05). Normal saline (sham protocol) produced no change in any parameter.The data indicate that fetal blood levels of AVP and AVT can influence transplacental water flow. Fetal AVP infusion produces a net gain in fetal water by inhibiting baseline fetal to maternal water flow. Both AVP and AVT infusion inhibit fetal to maternal water transfer after an osmotic stimulus to the ewe.

Fetal Arginine Vasopressin under Basal and Hypoosmolal Conditions

Blood samples (4 ml) for plasma arginine vasopressin (AVP) measurements were obtained at 3- to 4-hour intervals under basal conditions for 1-2 days from 5 date-bred ewes with chronic maternal and fetal vascular catheters. In addition, 6 chronically catheterized ewes were infused with 2 liters of 0.45% NaCl over 30 min. Fetal and maternal blood samples were obtained before and after the infusion period for measurement of plasma osmolality and AVP concentrations. In the first study, maternal and fetal plasma AVP levels correlated significantly (p less than 0.01, by linear regression analysis) under basal conditions. In the second study, baseline mean (+/- SEM) plasma osmolality was similar for pregnant ewes and fetuses (303 +/- 3.1 and 302 +/- 2.4 mosm/kg, respectively). There was a significant (each, p less than 0.01 by paired t test) decrease from baseline in maternal and fetal osmolality during the 30 min after completion of the hypotonic saline (to 292 +/- 4.7 and 296 +/- 2.4 mosm/kg, respectively). Fetal plasma AVP levels decreased 17 +/- 6% by 30 min following the completion of water loading (1.7 +/- 0.07 to 1.4 +/- 0.16 microU/ml; p less than 0.05). Maternal plasma AVP levels decreased 16 +/- 4% by 30 min after completion of infusion (1.6 +/- 0.14 to 1.38 +/- 0.6 microU/ml; p less than 0.05). These results indicate that maternal and fetal plasma AVP levels correlate under basal conditions and that maternal water loading, which significantly decreases fetal plasma osmolality, significantly suppresses fetal plasma AVP concentrations.

Permeability of the sheep placenta to 125I-arginine vasopressin.

We studied the permeability of the ovine placenta to AVP. 125I-AVP (9.3 +/- 1.9 mU) with approximately 82 (+/- 17.3) X 10(6) counts per 5 min were infused intravenously in 6 pregnant ewes. Six blood samples were collected at 10-min intervals over a 1-hour period from chronically catheterized maternal and fetal sheep. 125I-AVP in maternal and fetal plasma samples (1 ml each) were counted in a gammacounter for 5 min. Maternal counts decreased from 9,300 to 2,500 counts per 5 min over the hour following infusion but no increase in radioactivity could be measured in fetal blood, indicating that the sheep placenta is impermeable to 125I-AVP.

Arginine vasopressin metabolic clearance and production rates in fetal sheep, pregnant ewes, and lambs.

Arginine vasopressin (AVP) metabolic clearance rates (MCR) and production rates (PR) were measured in chronically catheterized fetuses, maternal ewes (130-135 days of gestation), and 1- to 6-month-old sheep using constant infusion noncompartmental kinetic methodology. No significant differences in mean basal plasma AVP levels, MCR rates or PR were found among the fetuses, maternal ewes or lambs. MCR of AVP did not change with steady-state plasma AVP levels varying from 2 to 68 micronmicron/ml. Neither the placenta nor the fetal kidney appear to play a significant role in AVP metabolic clearance.

Oxytocin release induced by melatonin in the ewe

The pineal gland indolamine melatonin now appears to be a primary mediator of the timing of estrus in mammals. Because the neurohypophyseal nonapeptides arginine vasotocin and oxytocin have recently been identified in the pineal glands of several species, we sought to assess the possibility of an interaction between melatonin and the neurohypophyseal hormones. An acute melatonin infusion (216 mumol) was administered to pregnant and nonpregnant ewes. Although plasma arginine vasopressin and arginine vasotocin levels did not change, melatonin produced a significant increase in plasma oxytocin in the nonpregnant though not the pregnant ewe. These data suggest a possible interaction between melatonin and oxytocin in the integration of mammalian reproduction cycles.