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To assess whether increases in circulating atrial natriuretic hormone (ANH) in response to the plasma volume expansion, besides the volume receptor-mediated mechanisms, attenuate the arginine vasopressin (AVP) response to increased plasma osmolality and whether changes in plasma AVP and ANH affect renal solute excretion under hypertonic plasma volume expansion, hypertonic saline (0.95 mol/l saline) alone, hypertonic saline with 6% dextran (6D-HS) and hypertonic saline with 9% dextran (9D-HS) were administered into anesthetized dogs. In the control study, 0.15 mol/l NaCI alone was administered. Plasma AVP and ANH and cardiovascular and renal functions were determined. Hypertonic saline and 9D-HS also were administered into the vagotomized and sham operated dogs, and the same parameters were determined. Mean blood pressure and heart rate never changed in all the groups, but central venous pressure and plasma volume increased markedly in 6D-HS and 9D-HS groups. In the control and hypertonic saline groups, central venous pressure increased slightly but plasma volume never changed. Plasma AVP increased in the order of hypertonic saline, 6D-HS and 9D-HS, but plasma ANH increased in reverse order. Vagotomy restored the AVP response to 9D-HS to 75% of its response to hypertonic saline, with a marked rise in plasma ANH. Urine sodium and potassium excretion and urine flow increased in hypertonic saline, 6D-HS and 9D-HS groups, but these increases were comparable among the groups. In the control group, these parameters never changed. These results suggest that the volume receptor-mediated vagal neural and ANH responses to the plasma volume expansion may have an effect on the suppression of the AVP response to osmotic stimuli, and increased plasma ANH release never potentiated the natriuresis under the hypertonic plasma volume expansion.

The regulation of anterior pituitary adrenocorticotropin hormone (ACTH) secretion during stress involves several hypothalamic neurohormones, including arginine vasopressin (AVP). In situ hybridization techniques have been used to study the regulation of neuropeptide messenger ribonucleic acids in the hypothalamus. Owing to the relatively slow time course of the changes in cytoplasmic messenger ribonucleic acid concentrations, rapid alterations in the level of neuropeptide gene transcription could not be detected. Because of its rapid processing, the nuclear level of the heteronuclear ribonucleic acid should reflect the rate of its synthesis, namely the transcription of the gene. We have used in situ hybridization with a probe complementary to a portion of an intronic sequence of the rat AVP gene to study rapid changes in the level of AVP gene transcription during emotional stress. The specificity of our technique was demonstrated by the localization of the hybridization signals in the paraventricular nucleus, the supraoptic nucleus and the suprachiasmatic nucleus, and was confirmed by the nuclear localization of the labeling. Isolation and exposure of male rats to a novel environment induced an activation of the pituitary-adrenal axis and an increase in AVP heteronuclear ribonucleic acid concentrations in the paraventricular nucleus 2 h after the onset of the stress, suggesting that an increased AVP gene transcription may play a role in the activation of the pituitary-adrenal axis in response to emotional stress.

In order to study the influence of the hypothalamic-pituitary-adrenal axis on the levels of endogenous digitalis-like substances (EDLS) in plasma and urine, eight healthy subjects (25–40 years old) were given dexamethasone 1 mg orally and tetracosactide (an ACTH analog) 0.25 mg iv, on separate occasions. The circulating levels of EDLS, TSH, PRL and AVP following administration of either test drug, and under control conditions, were measured by a RIA for digoxin and specific RIAs for each hormone. Plasma cortisol was measured by liquid chromatography. The area under the curve (AUC) of hormone levels between 08.00 and 09.30 was used for data comparisons. Urine was collected before and after each test dose, and analysed for cortisol levels by gas chromatography/mass spectrometry, and for digitalis-like activity both by RIA and by a bioassay measuring 86Rb-uptake into red blood cells. Dexamethasone suppressed the AUC of plasma and urine levels of cortisol (p=0.0001 and p86Rb-uptake assay was decreased, but not to a statistically significant degree. ACTH increased the levels of cortisol in plasma (p=0.0001) and urine (p

The effects of chronic and acute changes in plasma composition on the osmolality and sodium concentration of cerebrospinal fluid and plasma vasopressin (AVP) concentration have been examined. Chronic elevation of plasma osmolality in three strains of genetically AVP-deflcient rats (Brattleboro and New Zealand hypertensive and normotensive Brattleboro) was associated with increased cerebrospinal fluid osmolality by comparison with AVP-replete controls (Long Evans and New Zealand genetically hypertensive and normotensive rats). The linear correlation between plasma and cerebrospinal fluid osmolality did not reflect a similar relationship between plasma and cerebrospinal fluid sodium concentration. Hypertensive animals exhibited a threefold higher plasma AVP concentration in association with significantly elevated cerebrospinal fluid osmolality by comparison with normotensive controls. Although ip hypertonic saline injection elicited parallel increases in plasma and cerebrospinal fluid osmolality and sodium concentration in both hypertensive and normotensive rats, only in the normotensives did this result in an increase in plasma AVP concentration. These results indicate that cerebrospinal fluid is subject to modest chronic and acute changes in osmolality and sodium concentration which may contribute to the osmotic control of AVP secretion. The disturbed control of vasopressin secretion in hypertensive rats may in part be related to the abnormal cerebrospinal fluid composition in these animals.

The influence of age on several parameters related to water balance was studied in Wistar rats. Plasma AVP concentration and plasma osmolality were increased at midday in 21-month-old rats as compared with 3- and 4-month-old rats. Daily water intake per 100 g body weight was reduced in 14- and 21-month-old rats as compared with 3- and 4-month-old rats, but total water intake was unaltered. These results suggest that there is a change in water balance in Wistar rats with age. In order to obtain information about the influence of age on daily fluctuations in plasma AVP concentration and osmolality these parameters were determined in 4-month-old Wistar rats sacrificed at 2 h intervals during the day and in 20- and 31-month-old rats sacrificed at 8 h intervals. Plasma AVP concentrations were low during the light period and high during the dark period in 4-month-old rats. The relationship between plasma osmolality and plasma AVP concentration was dependent on the time of day in 4-month-old-rats, Plasma AVP concentrations were higher at 16.00 than at 08.00 and 24.00 in 20-month-old rats, and higher at 24.00 than at 08.00 and 16.00 in 31-month-old rats. In contrast to the plasma AVP concentration during the light period, the average daily AVP concentration (average of plasma AVP concentrations at 08.00, 16.00 and 24.00) was increased in 31-month-old rats only. The relationship between plasma osmolality and plasma AVP concentration was not age-related. The results of the present study suggest that there is a circadian rhythm of plasma AVP concentration in Wistar rats which is age-related but which does not fully correlate with plasma osmolality.

Arginine vasopressin stimulates the secretion of adrenocorticotropin. A direct stimulatory effect of AVP on cortisol as well as aldosteron secretion has been postulated by several investigators. To study the possible role of a direct stimulatory action of AVP on the adrenal cortex, normal volunteers were treated with incremental injections of ACTH or with incremental infusions of AVP which raised plasma AVP levels to a maximum of 256±16 pmol/l. In both situations, a significant (p0.5). Plasma aldosterone was stimulated by both treatments, but the weakly positive correlation between plasma ACTH and plasma aldosterone was not significant for either stimulus. Thus, in man, a direct stimulatory effect of AVP on cortisol secretion cannot be demonstrated. A direct effect of AVP on aldosterone cannot be definitely excluded, but is certainly of minor importance.

Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 μg/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2±1.6 ng/l (3.8±0.35 pmol/l) to 31.7±4.2 ng/l (7.0±0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5±1.2 ng/l (3.6±0.26 pmol/l) to 41.8±3.5 ng/l) (9.2±0.77 pmol/l) being significant (p

Glucocorticoids are known to inhibit the AVP response to osmotic and hemodynamic stimuli in humans. In the present study, we examined whether the AVP response to other primary stimuli, such as insulin-induced hypoglycemia and cigarette smoking was sensitive to inhibition by dexamethasone. The plasma ACTH responses were also measured. Twenty-four normal men were randomly divided into 3 groups of 8 subjects. One group was tested with insulin (0.15 IU/kg in an iv bolus) and another group with cigarette smoking (2 non-filter cigarettes smoked in succession within 10 min) with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin or smoking). The third group was tested with dexamethasone alone (2 or 4 mg in an iv bolus). The administration of dexamethasone (2 or 4 mg) alone did not modify the circulating levels of AVP and ACTH at any time during the next hour. The hypoglycemic response to insulin was similar regardless of dexamethasone treatment. AVP rose sharply in response to both hypoglycemia and smoking, reaching mean peak levels at 45 and 30 min, respectively. After both stimuli, the mean peak levels of AVP were 2.25 times higher than baseline. Pretreatment with dexamethasone (2 or 4 mg) significantly decreased the AVP responses to both hypoglycemia and cigarette smoking. Following pretreatment with dexamethasone (2 or 4 mg) the AVP increments in response to hypoglycemia or cigarette smoking were only 1.7 times higher than baseline. The plasma concentrations of ACTH were strikingly increased by hypoglycemia. The mean peak level was 3.5 times higher than baseline and was reached at 45 min. Pretreatment with dexamethasone (2 or 4 mg) significantly reduced hypoglycemia-induced ACTH increase, with a mean peak response 2.8 times higher than baseline. Cigarette smoking significantly increased the plasma ACTH concentrations. The mean peak level was observed at 20 min and was 1.3 times higher than baseline. The ACTH response to smoking was not significant following pretreatment with dexamethasone (2 or 4 mg). These data show a partial inhibitory effect of dexamethasone on hypoglycemia-and cigarette smoking-stimulated AVP secretion. In addition, the data show suppression by dexamethasone of the ACTH response to cigarette smoking and confirm previous observations of a partial inhibition by glucocorticoids of hypoglycemia-induced ACTH release.

We studied the changes in plasma arginine vasopressin in 5 patients with diabetic ketoacidosis and one patient with non-ketotic hyperosmolar coma who had marked hyperglycemia (36.6 ± 4.6 mmol/l, mean ± sem) and dehydration. Plasma osmolality (Posm) was 342.2 ± 11.4 mOsm/kg H2O, and hematocrit, serum protein, and blood urea nitrogen were also elevated at hospitalization. Circulating blood volume was decreased by approximately 21% as compared with that on day 7. Plasma AVP level was increased to 8.5 ± 1.6 pmol/l at hospitalization. When hyperglycemia was improved by iv infusion of a small dose of insulin plus fluid administration, plasma AVP level promptly decreased to 2.4 ± 0.4 pmol/l within six hours. When plasma AVP level had normalized, Posm was still as high as 305 mOsm/kg H2O, but the loss of circulating blood volume was only 4.2% of the control state. Plasma AVP level was positively correlated with change in hematocrit (plasma AVP = 3.58 + 0.45 · hematocrit, r = 0.468, p < 0.01), serum protein (r = 0.487, p < 0.01), Posm (r = 0.388, p < 0.01), and blood glucose (r = 0.582, p < 0.01). Plasma AVP level was negatively correlated with the change in circulating blood volume (plasma AVP = 3.6 – 0.14 · change in circulating blood volume, r = −0.469, p

The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of β-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4–9) (1.44 fmol), Nα-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of β-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1–9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied β-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel β-endorphin-(1–31), the β-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lifes of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol β-endorphin-(1–31)) significantly enhanced the disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of β-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.

To investigate the role of dopamine receptors situated in the paraventricular nucleus and the anteroventral third ventricular region in regulating vasopressin release, responses of plasma AVP and its controlling factors to injections of dopamine into these regions and the lateral cerebral ventricle were examined in conscious rats. The injections of 156 nmol (30 μg) dopamine into the cerebral ventricle produced transient rises in plasma AVP 5 min later. When the dose of dopamine was reduced to 26 nmol (5 μg), the increase in plasma AVP was not provoked any more. However, injections of 26 nmol dopamine into the paraventricular nucleus greatly augmented plasma AVP 5 and 15 min later. This dose of dopamine was without effect on plasma AVP when injected into the anteroventral third ventricular region, including the organum vasculosum lamina terminalis, median preoptic nucleus, medial preoptic area and the periventricular preoptic nucleus. These dopamine administrations in the cerebral ventricle, paraventricular nucleus and the anteroventral third ventricular region did not significantly change AVP-controlling factors such as plasma osmolality, sodium and arterial pressure. On the basis of these results, we conclude that dopamine receptors in the paraventricular nucleus may function to facilitate AVP secretion, whereas those in the anteroventral third ventricular region may not play an important role in the regulation of AVP release.

The effects of rapid changes of circulating cortisol levels on ACTH secretion and on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) concentrations into hypophysial portal blood were studied in six adult rams. Pharmacological adrenalectomy was obtained by 3 h metyrapone infusion (100 mg·kg−1·h−1). Blockade of cortisol synthesis induced a tenfold increase of plasma ACTH levels accompanied by a moderate increase of CRF secretion (150% vs preinjection levels) and a large increment of AVP secretion (535% vs preinjection levels). ACTH levels remained high during the 3 h following the end of metyrapone infusion. During the same period, CRF secretion was still elevated (231% vs preinjection levels), while AVP secretion was further stimulated (2,151% vs preinjection levels). Subsequent hydrocortisone infusion (66 μg·kg−1·h−1) for 2 h induced a rapid decrease of both ACTH and AVP secretion, while CRF levels in hypophysial portal blood still remained elevated. These data suggest that changes in ACTH secretion induced by acute modifications of the negative glucocorticoid feedback are, in addition to the well documented direct effect of cortisol on the corticotropes, mainly mediated by variations of hypothalamic AVP secretion.

The plasma membrane fraction of the uterus of the chicken was found to contain a component that shows specific binding to arginine vasotocin (AVT), arginine vasopressin (AVP) and oxytocin (OT). This binding component possesses a higher affinity to AVT than to AVP or OT, and the affinity to AVT was higher in laying hens than in non-laying hens and immature pullets, while the maximum number of binding sites per mg protein was less in the laying hens. Intramuscular injections of either estradiol-17β, progesterone or testosterone into the immature pullets for six consecutive days caused an increase in the affinity and number of binding sites. The results suggest that AVT receptors are present in the chicken uterus and that their binding properties are affected by ovarian steroid hormones.

Ovarian extracts of Long-Evans rats separated using high performance liquid chromatography (HPLC) were measured by radioimmunoassays (RIAs) for the presence of oxytocin and arginine vasopressin (AVP). The results showed that the ovary contains both, and that they are indistinguishable from the respective standard synthetic peptides. During the estrous cycle, the ovarian content of oxytocin was 10-fold higher (p less than 0.01) in estrus than in the other phases, while AVP was 16- and 25-fold higher (p less than 0.01) in metestrus than in the other phases. In contrast, the plasma levels of oxytocin showed no significant difference among the various phases of the estrous cycle. However, the plasma level of AVP level was significantly higher (p less than 0.01) in diestrus than in other phases. The present study thus strongly supports the hypothesis that both oxytocin and AVP can be produced by the ovary itself in the rat. The possible roles of oxytocin and AVP in the reproductive cycle are discussed.

Plasma concentrations of endothelium-derived proteins (fibronectin and von Willebrand factor), liver synthesized proteins (haptoglobin, transferrin, ceruloplasmin, α1-antitrypsin, antithrombin III and factor VIII-coagulant) and plasma arginine-vasopressin (AVP) were measured in 12 hyperthyroid, 9 hypothyroid and 1 5 age- and sex-matched normal controls. In hyperthyroid patients the plasma concentrations of AVP and endothelium-associated proteins (EAP) were significantly higher than in the control group (p

To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism. an acute oral water load of 20 ml·kg−1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N= 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.

The adrenocorticotropin-releasing effect of arginine vasopressin is well known. The effects of AVP on other anterior pituitary hormones remain confusing, with few in vivo human data available. Two human studies of exogenous AVP effects on ACTH, GH, TSH and prolactin are described. In the dosage and route of administration used, AVP was found to be a specific ACTH secretagogue.

Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of α-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg iv insulin under control conditions, and during non-selective α-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6±0.8 pmol/l (mean ± sem) basally to a maximum of 2.5±0.8 pmol/l following hypoglycemia (p

In 9 dogs with pituitary-dependent hyperadrenocorticism and in 6 dogs with hyperfunctioning adrenocortical tumours, the osmoregulation of arginine vasopressin (AVP) release was investigated by iv infusion of 20% NaCl for 2 h at a rate of 0.03 ml per kg body weight. The responses were analysed in terms of sensitivity and threshold of the osmoregulation of AVP secretion. The sensitivity was normal in 6 dogs and lowered in 9. In 4 of the latter dogs there was complete absence of a response to hypertonicity. The osmotic threshold of AVP release was raised in 9 dogs and normal in 2 dogs, whereas in the four dogs without any response the term threshold was not applicable. The results were not different for dogs with pituitary-dependent hyperadrenocorticism and dogs with hyperfunctioning adrenocortical tumour. It is concluded that corticosteroid excess per se induces a marked impairment of the osmoregulation of AVP secretion. The loss of reactivity of the osmoreceptor system may contribute to the corticosteroid-induced polyuria, which is also the result of resistance to AVP in the kidney.

We studied the neurohypophyseal function of 20 patients with complete GH deficiency owing to pituitary stalk transection by means of the water deprivation and the hypertonic saline infusion test. In TI-weighted magnetic resonance images, high-signal intensity of the posterior lobe of the hypophysis was missing in all the patients. An ectopic posterior lobe was observed at the proximal stump of the transected stalk in 17 patients, whereas the 3 patients without ectopic posterior lobe had overt diabetes insipidus or intractable nocturnal enuresis. After water deprivation, 3 patients with large ectopic posterior lobes (length along the pituitary stalk axis exceeding 5 mm) showed urinary osmolality and plasma AVP levels as high as those of 13 patients with partial GH deficiency in whom magnetic resonance images revealed no abnormalities. On the other hand, 14 patients with small ectopic posterior lobes (length less than 5 mm) showed significantly lower urinary osmolality and plasma AVP levels than the patients with large ectopic posterior lobes (p

The regional distribution of immunoreactive OT and AVP in the human uterus was investigated. Specimens of non-pregnant human uterus and oviduct were homogenized and extracted. The tissue levels exceeded the plasma concentrations of the peptides. The largest quantities of both peptides were found in the cervix and oviductal isthmus. The amounts found in the uterine fundus and isthmus were, however, not significantly different. Only 23% of immunoreactive OT eluted in the position of standard peptide on high-performance liquid chromatography. All immunoreactive AVP eluted with standard AVP after additional ether extraction of octadecasilyl extracts. We conclude that the human uterus contains materials immunologically and chromatographically identical to oxytocin and vasopressin.

The effect of oxytocin on collagen metabolism in the cervix and lower uterine segment of pregnant women was studied by measuring the incorporation of [3H]proline in vitro. Oxytocin had a concentration related inhibitory effect on the labelling with [3H]proline. Addition of indomethacin did not influence the response to oxytocin indicating that the effect was not directly mediated by prostaglandins. Oestradiol-17β potentiated the effect of oxytocin. Vasopressin decreased the incorporation of [3H]proline slightly but the action of this hormone was significantly less than that of oxytocin. The results suggest that oxytocin under in vitro experimental conditions influences cervical connective tissue metabolism which is in contrast to current clinical experiences.

In order to examine the influence of carotid baroreceptor stimulation on arginine vasopressin secretion, 8 normal healthy males were subjected to static neck suction of −3.3 kPa for 20 min in the upright sitting position after overnight food and fluid restriction. The plasma concentration of arginine vasopressin did not change significantly during neck suction. However, in 3 subjects the termination of neck suction induced large increases in plasma arginine vasopressin from 1.8 to 63.7 ng/l, from 0.7 to 34.3 ng/l and from 2.1 to 19.0 ng/l, respectively. Two subjects experienced symptoms such as nausea and paleness during neck suction. Systolic arterial pressure increased slightly but significantly during neck suction from 15.3 ± 0.3 to 15.7 ± 0.4 kPa (N = 7, P < 0.05), whereas mean arterial pressure, diastolic arterial pressure, central venous pressure, heart rate, plasma osmolality, plasma sodium and potassium were unchanged. Haemoglobin concentration in blood and haematocrit increased significantly during and after neck suction, whereas plasma volume decreased. We conclude that neck suction with a negative pressure of 3.3 kPa in upright sitting man does not significantly affect plasma arginine vasopressin. However, termination of the stimulation induces large increases in some subjects. This may be explained by a direct effect on the vagus nerve or by a selective deloading of carotid baroreceptors.

This paper describes the production and evaluation of an antiserum with high affinity (Ka = 1.9 × 1011 l/mol) and specifity to 8-arginine-vasopressin (AVP). The antiserum binds only to the intact and unchanged ring and tail of the AVP-molecule. AVP was labelled with 125I by a modification of the chloramin T method and purified by gel-filtration. We describe the development and validation of a radioimmunoassay for AVP in human plasma and urine, using only one extraction method (octa-decasilyl-treated silica microcolumns) for both biological fluids. The overall sensitivity of the assay method is 0.3 pg/ml plasma and 0.6 pg/ml urine. Mean (± sd) plasma AVP-concentration in normally hydrated females was 1.2 ± 0.6 pg/ml (median 1.2 pg/ml) and 1.7 ± 0.7 pg/ml (median 1.8 pg/ml) in males. Mean urinary AVP excretion was 73 ± 43 ng/day with ad libitum water intake and normal activity. Sex differences were not statistically significant. We also assessed the response of plasma AVP and urinary AVP-excretion to waterload and dehydration.

Radioimmunoassay and chemical assay (high performance liquid chromatography (HPLC) with fluorescence detection) for arginine vasopressin (AVP) in purified synthetic preparations and in posterior lobe tissue samples (ox and rat) yielded essentially identical values. In tissue samples from the neurohypophysis, the reproducibility of the former method was roughly twice as good. The routinely used blood pressure bioassay was very poorly reproducible and yielded values deviating from the two other methods. In all three assays, the coefficient of variation was roughly five times higher in tissue samples than in synthetic preparations. It is suggested that a chemical rather than a biological assay is used for standardization of AVP for radioimmunoassay. Large differences were found in the quality of AVP preparations potentially usable as standards and tracers (after iodination) for radioimmunoassay. All commercial preparations should therefore be checked for their AVP and impurity content by high performance liquid chromatography.

The role of opioids in the regulation of arginine vasopressin release from the posterior pituitary is a subject of controversy. In the present study, we examined the effects of central administration of met-enkephalin, leu-enkephalin, the enkephalin analogue FK-33824, and the opiate antagonist naloxone, and the effects of systemic administration of met-enkephalin and FK-33824 on AVP secretion in conscious normal sheep. Intracerebroventricular infusion of FK-33824 significantly increased the plasma concentration of immunore-active AVP in a dose-dependent manner, but met-enkephalin, leu-enkephalin and naloxone failed to change plasma concentration of AVP. Intravenous infusion of met-enkephalin and FK-33824 also failed to change plasma concentration of AVP. The opiate antagonist naloxone given both centrally and systemically attenuated the increase in plasma concentration of AVP induced by FK-33824. We conclude that basal AVP release is stimulated by central administration of FK-33824.

Ovine corticotropin-releasing hormone (1 μg/kg body weight) and arginine vasopressin (1 μg/kg) were injected iv in sheep, both separately and in combination. Plasma were sampled just before and 5, 15 and 30 min after the injection. Adrenocorticotropin-related peptides were isolated by Sephadex G-50 column chromatography and measured by RIA. Cortisol and aldosterone were determined on the same plasma samples. Three molecular forms of immunoreactive ACTH (IR-ACTH) were isolated: 'big' (> 20 000 mol wt), 'intermediate' (= 8000 mol wt) and 'little' (= 4500 mol wt). Following CRH injections, the three molecular forms of ACTH were enhanced, particularly the 'little' form, whereas 'intermediate' IR-ACTH was highly and specifically responsive to AVP. After a simultaneous injection of CRH and AVP, additive increases occurred for 'intermediate' and 'little' IR-ACTH. The release of different molecular forms of IR-ACTH after stimulation by CRH or AVP of corticotrope cells suggests that ACTH-related peptides could be stored in different intracellular pools or secreted by different pituitary cells.

The effect of desglycinamide9-[Arg8]-vasopressin (DGAVP) on memory processes was studied in patients with Korsakoff's syndrome. Intranasal treatment with DGAVP for 7 days affected neither attention nor short- and long-term memories. It is suggested that treatment with DGAVP is not indicated for all types of memory disorders, and that the beneficial effect of this treatment may depend on the integrity of certain brain structures.

The excretion of vasopressin in urine from healthy human subjects under different stages of hydration was estimated in urine extracts by bioassay (rat antidiuresis) and radioimmunoassay. In normally hydrated subjects the excretion was 490 ± 164 μU/h and 430 ± 133 μU/h for bioassay and radioimmunoassay respectively (mean ± sem, n = 5). After total fluid restriction for 10 to 12 h the excretion increased to 1370 ± 329 μU/h for bioassay and 1163 ± 279 μU/h for radioimmunoassay (mean ± sem, n = 6). An oral water load (25 ml/kg) reduced the value to 169 μU/h (bioassay) and 118 μU/h (radioimmunoassay) (mean, n = 2). In general the biological estimations were 20 % higher than the immunological estimations (P < 0.01). The urinary vasopressin excretion was positively correlated to urine osmolality. Synthetic arginine vasopressin (AVP) and urine extracts were both heterogeneous in ion exchange chromatography. The immunoreactive material was always eluted in 2 peaks, situated at the same places in the elution diagram. The material in the second peak was biologically active. The first peak from the AVP standard was biologically inactive, whereas the same peak from urine extract was active. This peak was shown to be an artefact formed during the extraction procedure.

A syndrome of periodic catecholamine and prostaglandin E2 discharge is described in 2 patients aged 17 and 3 years. They had recurrent attacks of vomiting, hypertension and psychotic depression for several years with a fixed periodicity. At initiation of the attack, plasma ACTH, AVP, norepinephrine and prostaglandin E2 were markedly elevated, whereas dopamine was undetectable. This resulted in hypercortisolemia, hyponatremia and oliguria, which were completely normalized when the attack subsided. Dopaminergic inhibition by metoclopramide injection induced a sustained rise in plasma bicyclo-prostaglandin E2 in the patients, a transient rise in 4 controls, and no response in 8 control children. The 4 control responders had significantly higher plasma norepinephrine levels and aldosterone responses than the non-responders (P < 0.001). There was a linear correlation between peak values of bicyclo-prostaglandin E2 and basal norepinephrine levels (r = 0.990, P < 0.001). The patients released bicyclo-prostaglandin E2 and aldosterone more easily than the control responders in terms of plasma norepinephrine and dopamine levels. Treatment of the patient with clonidine was partially effective, whereas administration of indomethacin completely suppressed recurrence of the attacks for 1 year. These results suggest the etiologic possibility that the patients have a decreased dopaminergic inhibition of prostaglandin E2-mediated norepinephrine secretion, which causes periodic discharge of norepinephrine and concomitant release of ACTH and AVP.

Studies were performed to determine the effects of neurotransmitters on arginine vasotocin (AVT) release in vitro. Rat pineal glands were incubated with 10−8m or 10−6m norepinephrine (NE), dopamine (DA), serotonin (5HT), and acetylcholine (ACH) for eight h after which the concentrations of AVT in the media were determined by radioimmunoassay. With the exception of ACH, none of the neurotransmitters had a significant effect on AVT release. ACH significantly (P < 0.05) elevated AVT release in vitro at the 10−6m concentration but not at the 10−8m concentration. The data indicate that ACH may play a role in the regulation of rat pineal gland secretion of AVT in vitro.

Arginine vasopressin responses to osmotic (0.1 ml · kg−1 · min−1 NaCl), orthostatic (standing upright and maintenance of orthostatic position for 20 min), and hypoglycemic (0.15 IU/kg insulin) stimuli were evaluated in women with polycystic ovaries and in normal subjects. Blood dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, testosterone, cortisol, and endogenous insulin levels were significantly higher in women with polycystic ovaries than in controls, whereas estrone, estradiol-17β, progesterone and 17OH-progesterone concentrations were normal in all subjects. Arginine vasopressin basal levels (mean ± sem of 3 test days; women with polycystic ovaries: 2.8 ± 0.2 pmol/l; controls: 2.7 ± 0.2 pmol/l) and secretory responses to orthostatic (mean peaks 100% higher than baseline values) and to hypertonic (130% increments) stimuli were similar in the two groups. Arginine vasopressin responses to hypoglycemia were lower in women with polycystic ovaries (50% increment) than in controls (150% increment), although comparable blood glucose decrements and GH or cortisol increments were found in the two groups. Arginine vasopressin peak responses to hypoglycemia were negatively correlated to testosterone, androstenedione, and endogenous insulin levels, but did not correlate with basal and hypoglycemia-induced peak cortisol concentrations or with circulating levels of other steroids. These data indicate a hypothalamic posterior pituitary disorder affecting arginine vasopressin response to insulin-induced hypoglycemia in women with polycystic ovaries syndrome associated with elevated blood androgen and insulin concentrations.

To evaluate a central role of angiotensin in vasopressin (ADH) release in response to hyperosmolality or hypovolaemia, we examined in conscious rats the effects of intraperitoneal (ip) injections of 2 ml/100 g body weight of hypertonic saline or polyethylene glycol (PEG; 250 mg/ml of 145 mM NaCl) on plasma ADH and angiotensin II (AII) levels and of intracerebroventricular (icv) administrations of Sar1-Ala8-AII (a competitive receptor blocker for AII) on the plasma ADH responses to the ip injections. Thirty min after ip injections of 900 mm NaCl, plasma ADH, osmolality and sodium increased with unchanged plasma AII and with reduced haematocrit. Two h after ip administrations of PEG, plasma ADH, AII and haematocrit were augmented with un-altered plasma osmolality and sodium. The responses of plasma ADH to ip injections of 900 mM NaCl and PEG were significantly inhibited (P < 0.05) by 1 μg of Sar1-Ala8-AII injected icv 5 min before blood samplings which had no appreciable effect on plasma osmolality, electrolytes and haematocrit. Based on these results, we concluded that angiotensin may participate in both the hyperosmolality- and hypovolaemia-induced ADH secretion by acting on the central nervous system.

The plasma arginine vasopressin concentration (pAVP) was measured in blood samples obtained from an internal jugular vein of 8 patients who under-went surgery for a carotid artery stenosis. Ten blood samples were taken with 1 min interval during the operation. Arterial pAVP was measured in 10 simultaneous samples from a radial artery and the brain veno-arterial difference of pAVP was calculated. The veno-arterial difference was 0–3 pg/ml in 7 of the patients, while it increased to 35 pg/ml upon baroreceptor stimulation in one patient. A pulsatile pattern was found in the veno-arterial difference of pAVP both at low and higher peripheral pAVP levels. This appeared to reflect a discontinuous release of AVP from the neurohypophysis. The described method results in a more accurate picture of ongoing secretory activity than can be obtained by measurements of peripheral pAVP alone. The general usefulness of the method, however, is restricted by the need of a multitude of samples and the difficult approach to the internal jugular vein.

Renal electrolyte excretion has been examined in water loaded ethanol anaesthetised rats receiving continuous iv saline (0.077 m NaCl) infusion. These animals exhibited very low rates of Na+, K+ and Cl− excretion by comparison with Inactin anaesthetised rats. Water loaded Inactin anaesthetised rats also showed a degree of Na retention but both Na+ and K+ excretory rates were higher than in ethanol anaesthetised animals. Plasma aldosterone levels did not differ between ethanol and Inactin anaesthetised groups. Vasopressin administration did not effect Na+ but potentiated K+ excretion in ethanol anaesthetised animals. This contrasted with the potent natriuretic and weak kaliuretic action of vasopressin in water loaded Inactin anaesthetised rats. The significance of abnormal renal electrolyte handling and the marked kaliuretic effect of vasopressin to the use of ethanol anaesthetised animals for vasopressin bioassay is discussed.

In order to study the effect of atrial tachycardia on the release of atrial natriuretic peptide (ANP), AVP, and methionine enkephalin (M-Enk), plasma concentrations of these peptides in the right ventricle were determined in patients with various arrhythmias (N = 10) during cardiac catheterization and incremental atrial pacing. Each pacing (100 per min, the maximum rate for 1:1 atrioventricular conduction, and 200 per min) lasted 4 to 5 min. Plasma ANP was significantly increased from 53.1 ± 12.2 in the resting condition to 168.9 ± 59.9 pmol/l at a pacing rate of 200 beats per min (P < 0.05); plasma AVP tended to decrease, but not significantly, and plasma M-Enk did not change at all. Pulse pressure in the right atrium (PPRA) and mean right atrial pressure (MRAP) tended to increase during the pacing, and at the rate of 200 beats per min PPRA was significantly higher than at the rate of 100 beats per min. Mean arterial blood pressure, plasma osmolality, and plasma sodium and potassium concentrations did not change significantly. There were significant correlations between plasma ANP and PPRA, MRAP and heart rate. These results indicate that atrial pacing stimulates ANP release with a rise in right atrial pressure, but does not influence M-Enk and AVP releases.

In response to different stress stimuli the foetal neurohypophysis releases arginine vasopressin (AVP). Part of the AVP is cleared from circulation by urinary excretion into the amniotic fluid (AF). Increased AF AVP levels may therefore indicate foetal stress, all the more because AF AVP solely is of foetal origin. We therefore studied AF AVP levels in 13 patients with rhesus erythroblastosis from 22 to 34 weeks of gestation. Twenty-eight patients from 14 to 34 weeks of gestation served as controls. The AVP levels were measured by RIA. Spectral absorption curves were performed and delta/E values determined at 450 nm. Mean AF AVP levels in controls were 2.39 pg/ml and were not normally distributed. There was no significant change in AF AVP levels with different gestational age. If in rhesus erythroblastosis patients the delta/E value was low (n = 7; × = 0.048 ± 0.007 se), the AF AVP values were not increased. If the delta/E values were within zone III (n = 6; × = 0.22 ± 0.035 se), indicating severe haemolysis, the AF AVP levels were significantly elevated (4.7 pg/ml ± 0.51 se; P = 0.001). Linear regression analysis showed a significant correlation between delta/E and AF AVP values (P = 0.05; y = 1.94 ± 10.88 x). We conclude that there is evidence for the role of AF AVP as a marker for foetal stress in rhesus erythroblastosis.

Intranasal treatment with desglycinamide9-(Arg8)-vasopressin (DGAVP) improved certain aspects of cognitive functions of patients with acquired and congenital diabetes insipidus and of alcoholic patients with mild cognitive impairments. Patients with Korsakoff's syndrome, presenting with severe cognitive impairments, were resistent to DGVP treatment. DGAVP treatment did not affect blood pressure and water metabolism. The action of DGAVP on cognitive functions is probably mediated by centrally located target sites and may be expressed only in patients in whom these target sites are unimpaired.

Two groups of six healthy young males participated in separate experiments to examine the physiological role of endogenous vasopressin in h-CRH-induced (100 μg iv) ACTH release: a) after drinking of 3500 ml of water; b) after thirsting for 23 h; c) after 0.9% saline infusion, and d) after 5.0% saline infusion (0.06 ml/kg per min for 120 min). AVP levels were markedly elevated (4 ng/l) after thirsting and 5% saline infusion when compared with water loading or infusion of physiological saline. Although basal and h-CRH-stimulated ACTH and cortisol levels tended to be higher during hypertonic saline infusion and dehydration, no significant difference was observed between states of high or low endogenous AVP levels. These results are not in accordance with previous studies using ovine CRH, which might be due to its longer half-time or the timing of the changes in AVP plasma levels in relation to the CRH injection. Our data suggest that the osmotic modulation performed in this study results in AVP concentrations in the adenohypophysis, which are in the threshold range for influencing ACTH release induced by exogenous h-CRH.

The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.

Two cases of hereditary diabetes insipidus (DI) are described, with an autopsy finding in one. The patients were brothers and 7 other relatives had symptoms of DI. The transmission of the disease in this family seemed to be an autosomal dominant trait with incomplete penetration. Both patients had the incomplete type of DI, which is diagnosed by the response of plasma AVP and the change in Uosm/Posm to 14 h water deprivation. The post-mortem examination in Case 1 showed that there was no atrophy of the supraoptic nucleus and paraventricular nucleus, but immunohistochemical studies revealed, that the paraventricular nucleus scarcely had any vasopressin positive cells in contrast to an autopsy control. This finding suggests that there may be a congenital defect in AVP synthesis in some cases of hereditary DI.

A sensitive and specific radioimmunoassay for 1-deamino-8-d-arginine vasopressin (DDAVP) was developed. Plasma concentrations of DDAVP after intragastric administration were determined in non-fasted rats and a dose-related increase in plasma levels was obtained. The immunoidentity of plasma DDAVP and standard was established by high performance liquid chromatography (HPLC). Correlation of biological and immunological responses of DDAVP was assessed using the antidiuretic effect in the Brattleboro (diabetes insipidus) rat.

Two dogs with hyponatremia due to inappropriate arginine vasopressin (AVP) secretion are described. Threshold and sensitivity of AVP secretion were investigated by increasing plasma osmolality with hypertonic saline infusion. In one dog, osmoregulation of AVP secretion occurred at normal sensitivity but at a low threshold. The other dog had a relatively high plasma AVP concentration under (resting) hypotonic conditions with an otherwise normal response to increasing plasma tonicity. In the absence of evidence for associated disease, it is suggested that both dogs have an idiopathic form of the syndrome of inappropriate AVP secretion.

The aim of this study was to assess the influence of hormones known to regulate fluid and electrolyte balance on the release of antidiuretic hormone induced by raising serum osmolality. The stimulus provoked by the infusion of a 2.5% NaCl solution induces an increase of urinary [arginine-8]vasopressin from 1.12 to 2.64 ng/h in men and from 1.65 to 7.27 ng/h in women as has been previously reported. These results were compared to those obtained in males infused with angiotensin II (All) before and during a hypertonic sodium load and in males infused with hypertonic saline on the fourth day of administration of ethinyl-oestradiol. During the combined infusion of All and then hypertonic saline, the mean hourly urinary excretion of AVP increased from 2.8 to 5.67 ng/h. Within each group the increase of urinary AVP was highly significant. The rise of urinary AVP during All infusion was significantly different from the rise observed both in untreated males and untreated females, lying in between. The mean hourly excretion rate of AVP increased before and after hypertonic saline loading from 2.65 to 5.3 ng/h in males pre-treated with ethinyl-oestradiol. The significant difference observed between males and females is reduced when males treated with oestrogen were compared to female subjects. In each group plasma renin activity decreased to low values during the salt-loading test. During oestrogen treatment PRA and plasma renin substrate rose, while urinary aldosterone remained almost unchanged. We conclude that All stimulates the release of AVP in males and potentiates the response of AVP to the osmolar stimulus, and that oestrogen potentiates in man the release of AVP in response to the osmolar stimulus. This oestrogenic effect may account for the observed sex difference.

The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P < 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 ± 0.2 pg/ml, P < 0.01 mean ± sem) than before the sauna (1.0 ± 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr-(Me)AVP (5 μg/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.

Direct measurement of plasma AVP and indirect assessment of antidiuretic activity during standard dehydration tests were made in 21 polyuric and polydipsic paients to establish the efficacy of each method in determining the cause of polyuria. Patients with acquired nephrogenic diabetes insipidus (e.g. diabetes mellitus, renal failure, hypercalcaemia) were excluded from the study. Cranial diabetes insipidus was diagnosed by plasma AVP responses to osmotic stimulation during infusion of hypertonic 5% saline which were subnormal in 13 patients, 4 of whom had undetectable plasma AVP and 3 who had reduced but osmoregulated AVP release. Standard water deprivation tests confirmed cranial diabetes insipidus in all but 2 patients who were diagnosed as partial nephrogenic diabetes insipidus. The remaining 8 patients had normal, osmoregulated AVP secretion; the cause of their polyuria was determined by their renal response to desmopressin. Two patients had nephrogenic diabetes insipidus and 6 had primary polydipsia. The majority of polyuric patients could be accurately diagnosed by carefully performed dehydration tests. We suggest that direct measurements of plasma AVP during osmotic stimulation are only necessary to distinguish mild forms of cranial from nephrogenic diabetes, or to define precisely the characteristics of AVP secretion.

To evaluate the roles for catecholamines in angiotensin II (ANG II)-induced vasopressin (AVP) release, we examined in conscious rats the effects of intraventricular (ivt) administrations of catecholamine antagonists on plasma AVP responses to ivt applications of its agonists and ANG II. Plasma AVP was determined by RIA using trunk blood collected after decapitation. Dopamine (0.15 μmol), phenylephrine (an alpha-adrenergic agonist, 0.15 μmol) or ANG II (48.2 pmol) augmented plasma AVP 90 sec after the injection, whereas after isoproterenol (a beta-adrenergic agonist, 0.15 μmol) plasma AVP was unaffected. The plasma AVP responses to both dopamine and ANG II were significantly (P < 0.01) inhibited by haloperidol (a dopamine blocker, 0.15 μmol) given 10 min before administration of these agents. Pre-administration of phenoxybenzamine (an alpha antagonist, 0.15 μmol) which was confirmed to abolish the effect of phenylephrine, or propranolol (a beta antagonist, 0.15 μmol) did not block the effect of ANG II. Administration of haloperidol, phenoxybenzamine or propranolol alone was without effect on plasma AVP level. On the basis of these results, we concluded that ANG II-induced AVP secretion may be mediated and/or modulated by dopamine.

In this study we have identified and characterized several vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion and oat cell carcinoma of the lung. Immunoreactive plasma vasopressin was measured after gel filtration (Sephadex G-25) or C-18 cartridge extraction using two different region-specific antisera: AS1 and AS2. Antiserum AS1 is more specifically directed towards the antigenic site of the hexapeptidic ring of arginine-vasopressin (AVP), whereas AS2 is more specifically directed towards the C-terminal region of AVP. Unexpectedly, the Sephadex G-25 gel filtration elution profile of the immunoreactive vasopressin was very heterogeneous, indicating the presence of several molecular species. After extraction of total AVP and AVP-like peptides of this plasma, an unusual AS1/AS2 ratio of immunoreactivity was observed, suggesting the presence of vasopressin-like peptides which differ from AVP in the C-terminus.

The role of arginine vasopressin (AVP) in the regulation of oxytocin secretion was studied in a superfusion system of the hypothalamo-pituitary complex from cycling female rats in dioestrus of the oestrous cycle. After perfusion with Medium 199 alone at 37°C for an equilibration period of 2.5 h, perfusion with Medium 199 containing 10 mU/ml AVP for 30 min caused a prompt and significant (P < 0.05) decrease in the oxytocin level of up to 60% of that before AVP perfusion, whereas Medium 199 containing 0.1 mU/ml AVP had no effect on oxytocin efflux. This finding suggests that AVP may be involved in the regulation of oxytocin release from the hypothalamo-pituitary system.

Several studies have indicated that arginine vasotocin (AVT), a nonapeptide closely related to vasopressin (ADH) and oxytocin (OT), may act as a pineal antigonadotrophic factor. The present studies were designed to investigate the effects of AVT on the luteinizing hormone (LH) and prolactin (Prl) release induced by sequential steroid priming of ovariectomized (OVX). rats. Sprague-Dawley rats were used 6–8 weeks post-OVX. After implantation of an intra-atrial bleeding catheter, animals were primed with 5 μg of oestradiol benzoate (EB) at 08.00 h on the next morning. Forty-eight hours later 1.5 mg of progesterone (P) was injected and animals were divided into groups which received either saline, AVT (1 of 4 doses), ADH, or OT. The saline or peptides were infused via the intra-atrial catheter at 10.00, 11.00, 12.00, and 13.00 h. Hourly blood sampling was performed at 11.00–18.00 h, and at 21.00 h. The 11.00, 12.00, and 13.00 h samples were taken 10 min after saline or peptide infusion. LH and Prl responses to the peptide infusions could be divided into pre-surge and surge effects. AVT caused a slight, but significant elevation of the normally low levels of LH and Prl which occurred before the onset of their surges. Only the highest dose of AVT (1.0 μg) blocked the LH surge. ADH, however, was capable of stimulating LH and Prl release during the pre-surge period and of inhibiting the LH surge. AVT at a dose of 0.5 or 1.0 μg specifically blocked the onset of the Prl surge, causing Prl to drop to its lowest level at 14.00 h - the time at which Prl levels were maximal in saline-treated animals. After this initial inhibition, however, Prl levels rebounded to show a delayed surge. OT infusion, on the other hand, caused a significant augmentation of the Prl surge. These data indicate that AVT may specifically block the onset of the Prl surge seen after sequential steroid priming of OVX rats, while OT may facilitate the Prl surge.