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Studies on the mode of action of vasopressin on the isolated proximal colon of the guinea-pig.

1. Contractions of guinea-pig isolated proximal colon produced by vasopressin are not affected by methyloxytocin (a compound that blocks pressor effects of vasopressin).2. Vasopressin contractions are inhibited by replacement of sodium with mannitol or sucrose, elevation of potassium or magnesium concentrations, the presence of the metabolic inhibitors sodium azide and triethyl tin or tetrodotoxin in the bathing fluid. Contractions produced by histamine or choline esters are comparatively insensitive to these procedures.3. Contractions of rat isolated uterus following vasopressin, oxytocin and methacholine are equally affected by replacement of sodium, increase of potassium or magnesium or addition of sodium azide.4. Neither vasopressin contractions nor contractions caused by transmural stimulation were consistently affected by morphine (10(-6) g/ml.) or hyoscine (10(-7) g/ml.) although both were reduced by anoxia or cooling the tissue. Morphine did not reduce the output of acetylcholine from stimulated colon.5. It is concluded that the action of vasopressin on proximal colon is unlike its action on other smooth muscle and is mediated by nervous tissue.

Acetylcholine↗

Vasopressin release by nicotine: the site of action.

1. In cats anaesthetized with chloralose the release of neurohypophysial hormones was examined after injection of nicotine into the cerebral ventricles or cisterna magna or its topical application through perspex rings to the ventral surface of the brain stem. The release was measured by assaying the hormones in samples of venous blood. 2. Injected into a lateral or the third cerebral ventricle, nicotine (0.5 to 1 mg) produced release of vasopressin without oxytocin. When the aqueduct was cannulated, preventing access to the fourth ventricle and to the subarachnoid space, this release did not occur. 3. Vasopressin was also released without oxytocin when nicotine (0.25 to 2 mg) was injected into the subarachnoid space through the cisterna magna. With this route of administration the nicotine did not enter any part of the ventricular system. 4. Applied through paired perspex rings placed across the ventral surface of the brain stem, nicotine again produced release of vasopressin without ocytocin. The amount of nicotine placed in each ring was usually 80 mug, but a release was obtained with 10 mug and in one experiment with as little as 5 mug. 5. The bilateral region on the ventral surface of the brain stem where nicotine acts when producing release of vasopressin lies lateral to the pyramids and in a longitudinal direction, 6 to 9 mm caudal to the trapezoid bodies. 6. The vasopressin release by nicotine injected intraventricularly or intracisternally, or applied topically to the ventral surface of the brain stem was not due to absorption of nicotine into the blood stream, nor to blood pressure effects. 7. It is concluded that nicotine acts on the ventral surface of the brain stem probably by activating the central projection to the supra-optic and possibly also the paraventricular nuclei of afferent pathways in the sinus and vagus nerves which control the release of vasopressin in response to changes in blood volume or distribution.

Administration, Topical↗

Central mechanism of vasopressin-induced changes in antidiuretic hormone release.

1. Intracerebroventricularly (i.c.v.) administered vasopressin (0.001-1.0 u) in dogs anaesthetized with chloralose produced adose-dependent increase in urine flow with a concomitant decrease in the levels of antidiuretic hormone (ADH) in jugular vein blood. 2. Higher doses of vasopressin (1.5-2.0 u, i.c.v) on the other hand had an antidiuretic effect and produced an increase in blood ADH level. 3. Pretreatment (i.c.v.) with a beta-adrenoceptor antagonist completely blocked the diuretic response of low doses of vasopressin (i.c.v.) but did not influence the antidiuretic response obtained with high doses. 4. Repeated administration of vasopressin (1.0 u, i.c.v.) induced tachyphylaxis; central catecholamine depletion with tetrabenazine significantly inhibited the vasopressin-induced diuretic response. 5. It is concluded that intracerebroventricular vasopressin-induced changes in ADH secretion are mediated through the release of catecholamines in the central nervous system.

Adrenalectomy↗

Influence of converting enzyme inhibition on the release of vasopressin induced by angiotensin.

1 The effects of intravenous infusion of angiotensin I, II and (des-1-Asp) angiotensin II (angiotensin III) on the plasma vasopressin levels, with and without converting enzyme inhibition, were investigated in conscious rats by use of a specific radioimmunoassay. 2 All three peptides caused a dose-dependent increase in vasopressin release, angiotensin III infusion being less effective than angiotensin I or II. 3 The converting enzyme inhibitor, SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) (1.0 mg/kg, i.v.), had no effect on the plasma vasopressin concentrations in bilaterally nephrectomized rats, but increased them in intact or sham-operated animals. 4 SQ 20881 potentiated vasopressin release, elicited by angiotensin I, leaving that elicited by angiotensin II unchanged. The receptor antagonist, saralasin, prevented the angiotensin-induced increase in plasma vasopressin concentration, even after pretreatment with SQ 20881. 5 These data support the assumption that the renin-angiotensin system may be involved in the control of vasopressin release, and indicate that in addition to angiotensin II, angiotensin I and III may also contribute, acting in concert.

Angiotensin II↗

Vasopressin-independent regulation of collecting duct aquaporin-2 in food deprivation.

BACKGROUND: Humans and animals are frequently subjected to food deprivation or starvation. However, the adaptation of the kidney to this condition is not well understood. The purpose of these studies was to examine the effects of food deprivation on water handling by the kidney, the expression levels of collecting duct (CD) water channel aquaporin-2 (AQP2), and to determine the role of vasopressin in the adaptation of AQP2 to food deprivation. METHODS: Sprague-Dawley (SD) and Brattleboro rats were placed in metabolic cages and deprived of food but had free access to water for 72 hours. Water balance and urine osmolality were measured daily. Kidney tissues were isolated and examined for the expression of AQP2 using semiquantitative immunoblotting and Northern hybridization. The circulating level of vasopressin and the mRNA expression levels of its precursor were determined by radioimmunoassay and Northern hybridization, respectively. RESULTS: In SD rats, the first 24 hours of food deprivation is associated with a significant polyuria and decreased urine osmolality (Uosm). This correlated with a significant down-regulation of AQP2 in the cortex and outer medulla. After 72 hours of food deprivation, Uosm increased above baseline, and urine volume dropped to a lower value. This was associated with a rebound increase in AQP2 expression in the cortex and OM and its up-regulation in the inner medulla. Interestingly, vasopressin mRNA expression and plasma levels were unchanged during food deprivation. Further, in homozygous Brattleboro rats, in which endogenous vasopressin is absent, food deprivation caused changes in urine volume, urine osmolality, and AQP2 expression, which are qualitatively similar to those observed in normal rats. CONCLUSION: Food deprivation impairs water handling by the kidney by causing dual changes in urine volume and urine osmolality. This effect is associated with parallel alterations in the expression of AQP2 and is independent of vasopressin activity. It is concluded that the increase in water reabsorption in the CD is an adaptive response of the kidney to a long period of food deprivation and is mediated via a vasopressin-independent mechanism.

Adrenal Cortex Hormones↗

Vasopressin response to dehydration in Alzheimer's disease.

Alzheimer's disease is a progressive deterioration of neuropsychological functioning. One of the main neuropathological correlates of the disease is a drop-out of cholinergic neurons within the central nervous system. The neuropeptide that is responsible for water homeostasis and defense against dehydration, vasopressin, is also under direct cholinergic control. Several studies have suggested that in Alzheimer's disease there has been a trend toward lower vasopressin levels than in age-matched controls. In order to improve discrimination of normal from diminished vasopressin levels, nine subjects with Alzheimer's disease (mean age 65 +/- 2 years) and nine age- and sex-matched controls (68 +/- 3 years) underwent a mild provocative challenge of overnight fluid restriction. Individuals with Alzheimer's disease had a greater degree of dehydration, with overnight serum osmolality of 313 +/- 4 vs 300 +/- 3 Mosmol/kg, P = .01, and diminished "thirst" as measured by water ingested in one hour of ad libitum water intake. Eight of the nine with Alzheimer's disease had levels of vasopressin which, by extrapolation, appear to be subnormal for their serum osmolalities, whereas seven of the nine control subjects has vasopressin levels within or above the reference range (P less than .05). Elderly individuals with Alzheimer's disease may be at increased risk of dehydration during periods of fluid restriction due to the loss of normal physiological responses of "thirst" and vasopressin secretion.

Aged↗

The effect of stimulation of atrial receptors on the plasma concentration of vasopressin.

The effect of stimulation of the left atrial receptors on plasma concentration of vasopressin and urine flow was studied in dogs anaesthetized with chloralose. Distending a large balloon in the left atrium, so as to occlude the mitral valve and increase left atrial pressure, consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. Discrete stimulation of the left atrial receptors, by distending small balloons in the pulmonary vein - left atrial junctions and in the left atrial appendage, consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. The left atrial receptors were stimulated discretely in dogs in which bretylium tosylate, atropine and atenolol had been administered. In these dogs distension of the small balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure and consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. It is concluded that this decrease in the plasma concentration of vasopressin is a direct result of discrete stimulation of the atrial receptors and is not secondary to any haemodynamic changes. The exact role of this decrease in plasma concentrations of vasopressin in the diuretic response to stimulation of the left atrial receptors remains to be established.

Animals↗

The effect of vasopressin on hormone secretion and blood flow from the thyroid vein in sheep with exteriorized thyroids.

1. Vasopressin has been shown to activate the thyroid in some species, and also to be released into the bloodstream after emotional and other stresses.2. Emotional stimuli applied to sheep have previously been shown to increase thyroid secretion and the possible influence of vasopressin in this process has been investigated. Sheep bearing exteriorized thyroid glands were used, so that thyroid vein blood could be collected in undisturbed conscious animals.3. (125)I or (131)I (50 muc) was injected I.M. into the sheep; 4-7 days later, samples of thyroid vein blood were collected at 10 min intervals for 4 hr, and the concentration of total and protein bound (125)I or (131)I was measured. Intravenous infusions of 0.3, 3.0 or 31 m-u./min arginine or lysine vasopressin, or close arterial infusions of 3.0 or 31 m-u./min arginine vasopressin were administered 1.5 hr after commencement of blood sampling. Blood flow from the thyroid was measured by a plethysmographic technique during similar experiments.4. No significant changes in thyroid hormone secretion were observed as a result of vasopressin infusion, and it was concluded that vasopressin release does not play a part in the activation of the thyroid resulting from emotional stimulus in the sheep.

Animals↗

The influence of vasopressin on hypothalamic corticotrophin releasing activity in rats with inherited diabetes insipidus.

1. The corticotrophin releasing activity of hypothalamic extracts from rats congenitally lacking vasopressin (Brattleboro strain) has been studied in the presence and absence of arginine vasopressin and its antiserum. 2. Hypothalamic extracts from Brattleboro rats stimulated the production of corticotrophin by pituitary segments in vitro but both their potency and the slopes of their dose-response lines were significantly less than those of controls. Arginine vasopressin also stimulated pituitary-adrenocorticotrophic activity in vitro but only in concentrations considerably greater than those present in hypothalamic extracts from normal rats. 3. In low, physiological concentrations arginine vasopressin did not affect the corticotrophin releasing activity of hypothalamic extracts from controls but potentiated markedly the activity of extracts from Brattleboro rats and rendered the slopes of their dose-response lines parallel with those of the controls. 4. The antiserum to arginine vasopressin did not affect the corticotrophin releasing activity of Brattleboro extracts but reduced the activity of control extracts and rendered the slopes of their dose-response lines parallel with those of Brattleboro extracts. 5. The results suggest that vasopressin acts synergistically with the corticotrophin releasing factor and is essential for the full expression of pituitary-adrenocorticotrophic activity.

Animals↗

Renal blood flow and its distribution following haemorrhage in the rat: the role of vasopressin.

The effect of an acute arterial haemorrhage of 15 ml/kg body weight on renal and intrarenal blood flow (measured using radioactive microspheres) was determined in anaesthetized rats. In order to assess the role of vasopressin in mediating the observed changes, the response to haemorrhage of animals lacking the ability to synthesize vasopressin (Brattleboro rats) was compared with that of the parent strain (Long Evans rats). In addition, a group of Long Evans rats was treated with an antagonist of the vascular action of vasopressin before being bled. Thirty minutes after haemorrhage the mean arterial blood pressure of untreated Long Evans rats was significantly higher than that of Brattleboro or vasopressin antagonist-treated Long Evans rats. Following haemorrhage, total renal vascular resistance increased markedly in untreated Long Evans rats. In these animals there were substantial increases in calculated vascular resistance in both inner and outer halves of the renal cortex. In Brattleboro rats there was only a small increase in renal vascular resistance, confined to the outer cortex, whilst in vasopressin antagonist-treated Long Evans rats there was no significant change in the vascular resistance of either cortical region. It is concluded that much of the increase in renal vascular resistance which follows haemorrhage is due to vasopressin. This vasoconstrictor effect of the hormone, which contributes to its pressor action after haemorrhage, occurs in both the inner and outer regions of the renal cortex.

Animals↗

The effects and interactions of angiotensin and vasopressin on the heart of unanaesthetized sheep.

The effects of infusions of angiotensin and vasopressin, in stepwise concentrations, on the cardiac baroreflex and on cardiac output were studied in seven adult unanaesthetized sheep and compared with those obtained with infusions of phenylephrine. Six animals were treated with the beta-adrenoceptor blocking drug, propranolol (in order to inhibit the effects of the sympathetic nervous system on the heart). One animal was not treated with propranolol. In those animals in which arterial pressure increased during infusion of vasopressin, the slope of the systolic pressure-pulse interval relation was greater than that seen when phenylephrine was used to increase arterial pressure. Compared with the cardiac response to pressor doses of phenylephrine, infusions of angiotensin were associated with a lesser degree of cardiac slowing and a lesser reduction in cardiac output. The effects of combined infusions of angiotensin and vasopressin on the cardiac baroreflex were studied. In five sheep which were infused with a pressor dose of angiotensin (1.1 microgram/min), the stimulatory effect of vasopressin (1.0 u./min) on pulse interval and its depressant effect on cardiac output were attenuated. In seven sheep infused with 0.5 u./min of vasopressin, I.V. infusion of angiotensin (0.2-5.0 micrograms), produced a progressive decrease in pulse interval and increase in cardiac output as the dose was increased. Therefore, angiotensin can offset the cardioinhibitory effects of vasopressin. Since cardiac sympathetic activity was blocked and neither drug has any direct chronotropic effect on the heart, it would appear that these interactions between the two drugs affect the cardiac vagus either at a peripheral or central level.

Angiotensin II↗

Inhibiting the rabbit caudal ventrolateral medulla prevents baroreceptor-initiated secretion of vasopressin.

The A 1 noradrenergic neurones are known to project from the caudal ventrolateral medulla to the vasopressin-secreting neuroendocrine cells in the hypothalamus. They therefore represent a possible central pathway from the medulla to the hypothalamus for baroreceptor-initiated secretion of vasopressin. We tested this hypothesis in the anaesthetized rabbit. Muscimol, a gamma-aminobutyric-acid-receptor agonist, was injected into the caudal ventrolateral medulla to inhibit the A 1 noradrenergic neurones. Secretion of vasopressin, measured by radioimmunoassay, was initiated either by arterial haemorrhage or by constriction of the inferior vena cava. After injection of vehicle into the caudal ventrolateral medulla, or after injection of muscimol into nearby control areas, both haemorrhage and constriction of the inferior vena cava produced the expected elevation in plasma vasopressin. After injection of muscimol into the caudal ventrolateral medulla, secretion of vasopressin in response to haemorrhage and to constriction of the inferior vena cava, was completely abolished. The A 1 noradrenergic neurones may be the sole pathway transmitting the reflex for baroreceptor-initiated secretion of vasopressin from the medulla to the hypothalamus.

Adrenergic Fibers↗

Stimulation of vasopressin release in the ventral septum of the rat brain suppresses prostaglandin E1 fever.

1. Infusion of prostaglandin E1 (PGE1) into a lateral cerebral ventricle of the rat evoked a rise in core temperature which could be attenuated by electrical stimulation of the bed nucleus of the stria terminalis (BST). Electrical stimulation of the BST in the absence of PGE1 did not alter body temperature in the afebrile rat. 2. When the intracerebroventricular (I.C.V.) infusion of PGE1 was preceded by a bilateral injection of saline or vasopressin V2 antagonist d(CH2)5D-ValVAVP into the ventral septal area (VSA), electrical stimulation of the BST suppressed the PGE1 hyperthermia. However, when the vasopressin V1 antagonist d(CH2)5Tyr(Me)AVP was injected into the VSA prior to I.C.V. infusion of PGE1, electrical stimulation of the BST did not alter the hyperthermic response to PGE1. 3. These actions were site specific in that the suppression of PGE1 hyperthermia was observed only when the electrode tips were located in the area of the BST. Similarly, the V1 antagonist only blocked the effect of electrical stimulation when injected into the VSA. 4. When the vasopressin V1 antagonist was injected into the VSA, the PGE1 fever was prolonged when compared to the controls with saline. 5. Injection of saline, vasopressin V1 and V2 antagonist into the VSA, without PGE1 or BST stimulation, did not evoke any significant change in the core temperature of the rats. 6. These data are consistent with the hypothesis that vasopressin may function within the brain as an endogenous antipyretic and that vasopressin may act in a BST-VSA neuronal pathway concerned with endogenous antipyresis.

Animals↗

Electrophysiological characteristics of immunochemically identified rat oxytocin and vasopressin neurones in vitro.

1. Intracellular recordings were made from supraoptic neurones in vitro from hypothalamic explants prepared from adult male rats. Neurones were injected with biotinylated markers, and of thirty-nine labelled neurones, nineteen were identified immunocytochemically as containing oxytocin-neurophysin and twenty as containing vasopressin-neurophysin. 2. Vasopressin and oxytocin neurones did not differ in their resting membrane potential, input resistance, membrane time constant, action potential height from threshold, action potential width at half-amplitude, and spike hyperpolarizing after-potential amplitude. Both cell types exhibited spike broadening during brief, evoked spike trains (6-8 spikes), but the degree of broadening was slightly greater for vasopressin neurones. When hyperpolarized below -75 mV, all but one neurone exhibited a transient outward rectification to depolarizing pulses, which delayed the occurrence of the first spike. 3. Both cell types exhibited a long after-hyperpolarizing potential (AHP) following brief spike trains evoked either with a square wave pulse or using 5 ms pulses in a train. There were no significant differences between cell types in the size of the AHP evoked with nine spikes, or in the time constant of its decay. The maximal AHP evoked by a 180 ms pulse was elicited by an average of twelve to thirteen spikes, and neither the size of this maximal AHP nor its time constant of decay were different for the two cell types. 4. In most oxytocin and vasopressin neurones the AHP, and concomitantly spike frequency adaptation, were markedly reduced by the bee venom apamin and by d-tubocurarine, known blockers of a Ca(2+)-mediated K+ conductance. However, a minority of neurones, of both cell types, were relatively resistant to both agents. 5. In untreated neurones, 55% of vasopressin neurones and 32% of oxytocin neurones exhibited a depolarizing after-potential (DAP) after individual spikes or, more commonly, after brief trains of spikes evoked with current pulses. For each neurone with a DAP, bursts of spikes could be evoked if the membrane potential was sufficiently depolarized such that the DAP reached spike threshold. In four out of five vasopressin neurones a DAP became evident only after pharmacological blockade of the AHP, whereas in six oxytocin neurones tested no such masking was found. 6. The firing patterns of neurones were examined at rest and after varying the membrane potential with continuous current injection. No identifying pattern was strictly associated with either cell type, and a substantial number of neurones were silent at rest.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

The effect of chloroquine on renal function and vasopressin secretion: a nitric oxide-dependent effect.

We have previously reported that chloroquine administration increases plasma vasopressin concentration and urinary sodium excretion in Sprague-Dawley rats. Because chloroquine has also been shown to stimulate nitric oxide production, the aim of this study was to determine whether nitric oxide mediates chloroquine-induced changes in renal function and secretion of vasopressin. Sprague-Dawley rats (n = 6-8/group) were infused with 2.5% dextrose under Intraval anesthesia (100 mg kg(-1) i.p.). After 3-h equilibration and a control hour, animals received either vehicle, chloroquine (0.04 mg h(-1)), N(omega)-nitro-L-arginine methyl ester (L-NAME) (nitric-oxide synthase inhibitor, 60 microg kg(-1) h(-1)), or combined chloroquine and L-NAME over the next hour. L-NAME or vehicle infusion continued for a further recovery hour. Plasma was collected from a parallel group of animals for vasopressin radioimmunoassay. Chloroquine stimulated a significant increase (p < 0.05) in urine flow rate, glomerular filtration rate, and sodium excretion over the hour of infusion, in comparison with vehicle-infused rats. These effects continued after cessation of chloroquine, reaching maxima in the following recovery hour. Coadministration of L-NAME abolished these effects, returning all parameters to levels comparable with those in vehicle-infused animals. Chloroquine administration was accompanied by a significant increase (p < 0.05) in plasma vasopressin, which was also reversed by L-NAME. The effects of chloroquine on renal function and vasopressin secretion seem to be mediated by pathways involving nitric oxide. These data suggest that chloroquine may stimulate nitric-oxide synthase both centrally, stimulating vasopressin secretion, and within the kidney, where it modulates glomerular hemodynamics and tubular function.

Animals↗

Cerebrospinal fluid vasopressin in neurological and psychiatric disorders.

Vasopressin was determined in CSF and plasma of 243 patients with different neurological and psychiatric disorders, including control patients. CSF vasopressin was significantly higher in patients with high pressure hydrocephalus, intracranial tumour, benign intracranial hypertension, intracranial haemorrhage, ischaemic stroke, and craniocerebral trauma. In patients with primary degenerative dementia, CSF vasopressin was lower than in control patients. Among patients with psychiatric disorders, CSF vasopressin was increased in manic patients, while in patients with depression CSF concentration of this hormone did not differ from that found in controls. However, an increase in CSF vasopressin level was found in patients recovering from a depression. The clinical significance of changes in CSF vasopressin concentrations in groups of patients with neurological and psychiatric disorders is still unknown.

Adult↗

Raised plasma arginine vasopressin concentrations during cluster headache attacks.

To obtain data about peripheral concentrations of arginine vasopressin in head pain syndromes, the plasma arginine vasopressin secretory pattern in 12 adult male patients with cluster headache was evaluated. Blood samples for plasma arginine vasopressin and osmolality determinations were collected before, and at 15, 30, 45, 60, 90, and 120 minutes during a cluster attack. Blood pressure was also monitored. The same sampling was repeated during an asymptomatic period. During cluster attacks, the mean values of plasma arginine vasopressin before an attack (2.3 (0.1) ng/l) significantly increased, reaching their peak at 45 minutes (4.8 (0.5) ng/l; P < 0.01 v baseline). No significant variations were found in mean arterial pressure and plasma osmolality. These data suggested involvement of neurotransmitter mechanisms regulating arginine vasopressin secretion and a possible role of arginine vasopressin in vasomotor phenomena accompanying cluster attacks.

Adult↗

Plasma vasopressin during increases and decreases in blood volume in anaesthetized dogs.

In chloralose-anaesthetized dogs, plasma vasopressin concentration was measured by radioimmunoassay during step changes in blood volume of 4 mL/kg over a range of blood volume from +20 to -12 mL/kg. Blood volume was both increased and decreased over this range. There was a logarithmic relationship between blood volume and plasma vasopressin concentration over the range of blood volume examined. There was also a logarithmic relationship between blood volume and mean left atrial pressure. Linear regression between the natural logarithm of plasma vasopressin concentration and mean arterial pressure, heart rate, and mean left atrial pressure gave the highest correlation coefficient (r = 0.94) between vasopressin and mean arterial pressure. The results support the hypothesis that there are sensitive mechanisms controlling the release of vasopressin in response to changes in blood volume. Observations were also made of changes in atrial pressure and activity of left atrial receptors during changes in blood volume over the same range. The results suggest that changes in atrial receptor activity are unlikely to be the major cause of the large increases in plasma vasopressin concentration associated with hypovolemia.

Anesthesia↗