The effect of hemorrhage and hypertonic saline upon plasma oxytocin and arginine vasopressin in conscious dogs.

Sensitive and highly specific RIAs for arginine vasopressin (AVP) and oxytocin (OT) were utilized to assess the specificity of neurohypophyseal hormone release after hemorrhage or infusion of hypertonic saline to trained conscious dogs. Phlebotomy of 12.5 and 25 ml/kg produced increases in plasma AVP from 1.0 +/- 0.2 to 7.8 +/- 2.1 and 41.6 +/- 9.7 (SEM) microunit/ml respectively, and both responses differed significantly from values in control experiments (P less than 0.01 after the first phlebotomy and P less than 0.001 after the second phlebotomy). Plasma OT concentrations rose from baseline values of 1.1 +/- 0.4 to 3.3 +/- 0.6 and 8.3 +/- 1.7 microunit/ml (P less than 0.005 and P less than 0.001 compared to controls); plasma osmolality and sodium concentrations were unchanged. Both log AVP and log OT were highly correlated with the quantity of blood removed (r = 0.92 and -0.82, each P less than 0.001). Infusion of hypertonic (20g/dl) NaCl (3.4 meq/kg) over 20 min caused plasma osmolality and sodium to rise from 304 +/- 1.0 mosm/kg and 143 +/- 3.0 meq/liter to 316 +/- 1.0 mosm/kg and 150 +/- 3.0 meq/liter (each P less than 0.001). Plasma AVP rose from 1.5 +/- 0.2 to 2.4 +/- 0.2 microunit/ml (P less than 0.0025) and OT rose from 1.2 +/- 0.5 to 2.6 +/- 0.7 microunit/ml (P less than 0.005). The stimulus response ratios (change in log hormone concentration divided by the rise in plasma osmolality) were comparable for both hormones (0.024 +/- 0.006 for AVP and 0.031 +/- 0.008 for OT; P less than 0.4). The data indicate that hemorrhage or hypertonic saline stimulate release of both AVP and OT. After hemorrhage, there is greater stimulation of AVP than OT, whereas there is comparable stimulation of both peptides after hypertonic saline.

Plasma norepinephrine, epinephrine, and dopamine concentrations in maternal and fetal sheep during spontaneous parturition and in premature sheep during cortisol-induced parturition.

The plasma catecholamine response to parturition was studied in two groups of chronically catheterized fetal sheep. Group I consisted of full term pregnancies with a mean gestation of 147 days at delivery. Group II was comprised of fetal sheep infused with cortisol to induce premature delivery at a mean gestational age of 135 days. Plasma catecholamine concentrations were measured in group I mothers and fetuses and group II fetuses by radioenzymatic assay using 50 microliter samples. Uterine contractions began 4--14 h before delivery in both groups. Significant increases in fetal plasma norepinephrine (NE) concentrations occurred within 3 h of delivery in both groups. Group I plasma epinephrine (E) and group I and II plasma dopamine levels were significantly increased within 1 h of delivery. Only plasma E levels differed in group I and II fetuses; there was no significant rise in plasma E concentrations in cortisol-infused (group II) fetuses. Maternal plasma NE and E concentrations were increased 2--3 h before delivery in group I animals. Maternal plasma dopamine concentrations were only elevated 30 min before delivery when plasma NE and E levels were highest.

Thyrotropin-releasing hormone stimulates release of arginine vasopressin and oxytocin in vivo.

The effects of TRH upon neurohypophyseal hormone release were studied in conscious rabbits. Intravenous infusion of 250 nm/kg TRH had no significant effect on either arginine vasopressin (AVP) or oxytocin (OT) release, but a 5-fold greater dose led to significant increases in plasma levels of both AVP and OT and behavioral arousal. Intraventricular injection of 3 nm TRH produced significant elevations of both plasma AVP and OT, with even greater effects on behavior than after iv infusion. The maximal hormone response to intraventricular injection was observed considerably earlier than that for iv injection and the response occurred after an almost 1000-fold lower dose of TRH. Neither artificial cerebrospinal fluid vehicle nor the inactive analogue D-tyrosine2 TRH (p-Glu-d-Tyr-Proamide) had any effect on neurohypophyseal hormone release or on behavior. MK-771 [L-N-(2-oxopiperidin-6-YL-carbonyl)-L-histidyl-L-thiazolidine-4-carboxamide], a TRH analog with enhanced central nervous system effects, had effects on AVP and OT release comparable to equimolar doses of TRH. TRH stimulates release of both AVP and OT after both intraventricular and iv injection, and these effects may be independent of behavioral activation.

Metabolic clearance rate and transplacental passage of oxytocin in the pregnant ewe and fetus.

The MCR and placental permeability to oxytocin were determined in chronically catheterized pregnant sheep. Simultaneous maternal and fetal plasma oxytocin (OT) concentrations were measured by RIA before and during continuous infusion of synthetic OT to steady state conditions. Baseline fetal plasma OT concentrations were significantly higher than simultaneously collected maternal concentrations (1.6 +/- 0.13 vs. 1.1 +/- 0.13 muU/ml, respectively; P less than 0.01). Mean fetal OT MCRs were 12.0 +/- 1.35 and 12.1 +/- 1.09 ml/kg . min at OT infusion rates of 64 and 640 muU/kg . min. Mean maternal MCRs were 12.1 +/- 2.64 and 12.4 +/- 1.38 ml/kg . min at OT infusion rates of 80 and 800 muU/kg . min. Uterine contractions were induced by maternal OT infusion of 800 muU/kg . min but not by lower infusion rates; no uterine contractions were induced by fetal OT infusion. OT did not appear to cross the placenta in either direction under the present study conditions.

Ovine maternal and fetal plasma oxytocin concentrations before and during parturition.

To study the relationships between fetal and maternal oxytocin (OT) levels and the initiation of labor in sheep, paired maternal and fetal plasma OT concentrations (microunits per ml) were measured by RIA. Samples were obtained daily from pregnant ewes and their fetuses for 5 days before spontaneous delivery and frequently during the first and second stages of labor and during the 3 h after delivery. The mean maternal plasma OT concentration during the first stage of labor was not different from that preceding labor. In contrast, the mean maternal plasma OT level during stage 2 of labor was significantly higher than the earlier baseline maternal values or the mean paired fetal concentration. There was no significant increase in the mean fetal plasma OT concentration before delivery. The newborn plasma OT concentration was elevated 15 min after delivery. From these data, we conclude that in the sheep, 1) the onset of labor is not associated with increased maternal plasma OT levels, 2) cervical or vaginal distension may be the stimulus for maternal OT release during stage 2 of labor, 3) an increase in the fetal plasma OT concentration does not occur before the initiation of labor or during the course of labor, and 4) stress in the final moments of labor or in early neonatal life may be responsible for elevated cord and early neonatal plasma OT levels.

Plasma oxytocin concentrations in men, nonpregnant women, and pregnant women before and during spontaneous labor.

Baseline plasma oxytocin (OT) concentrations were measured in 25 healthy men, 102 nonpregnant women, and 59 pregnant women from 15-42 weeks gestation. In addition, plasma OT levels were measured at the onset, peak, and immediately after a single uterine contraction in 6 women in the latent phase and 14 women in the active phases of labor, as well as in 19 women at initial presentation of the fetal head on the perineum (+3 station) and 11 women at the time of delivery of the head during a normal vaginal delivery. Baseline plasma OT concentrations did not vary significantly among men (1.5 +/- 0.2 microunits/ml), nonpregnant women (1.4 +/- 0.2 microunits/ml), or pregnant women before labor (1.3 +/- 0.1 microunits/ml) and did not differ in an additional subgroup of 20 women receiving oral contraceptive medication (1.8 +/- 0.7 microunits/ml). In studies conducted during labor, plasma OT concentrations did not correlate with uterine pressure measurements and did not increase significantly over baseline pregnancy concentrations during the latent (1.3 +/- 0.2 microunits/ml) or active (1.6 +/- 0.2 microunits/ml) phases of labor. There was a significant increase in plasma OT levels from the time of initial visualization of the fetal head to the time of delivery of the head (1.1 +/- 0.1 to 4.2 +/- 1.1 microunits/ml, respectively; P less than 0.05). These data support the view that maternal plasma OT levels remain low during pregnancy until late in the second stage of labor.

The effect of acute maternal hemorrhage on the release of catecholamines in the pregnant ewe and the fetus.

Five chronically instrumented pregnant ewes and their fetuses were studied to assess the effect of acute maternal hemorrhage. The hemorrhage was produced in two stages; during the first stage 15% of the total maternal blood volume was removed, and then in a second stage an additional 15% was removed. Biophysical and biochemical variables were monitored. Plasma dopamine, norepinephrine, and epinephrine were determined by a sensitive radioenzymatic assay. A significant rise in maternal and fetal catecholamines was observed following an estimated maternal blood volume depletion of 30%. During a 15-minute recovery period, the maternal catecholamine concentrations returned to normal, while the fetal concentrations remained elevated. These changes were accompanied by significant changes in maternal and fetal homeostasis. The significance of these findings is discussed.