Biomedical subjects

S L Lightman

Publications and source records attributed to S L Lightman.

At least 379 records · Page 21Linked to original sources

PubMed1987

Vasopressin activation of phosphatidylinositol metabolism in rat anterior pituitary in vitro and its modification by changes in the hypothalamo-pituitary-adrenal axis.

The ability of vasopressin to stimulate the accumulation of 3H-labelled inositol phosphates was studied in vitro using prelabelled rat anterior pituitary quarters. [8-Arginine] vasopressin activates inositol lipid breakdown in this system in a time- and dose-dependent manner; vasopressin (3 X 10(-7) M) resulted in a 1.8-fold stimulation of inositol phosphate accumulation over control accumulation after 10 min. This response to vasopressin is inhibited by the specific V1 antagonist (CH2)5Tyr(Me)AVP. Both oxytocin and the selective V2 agonist DDAVP also show some agonist activity, but are considerably less potent than arginine vasopressin. Corticotrophin-releasing factor alone had no effect on inositol phosphate production, whilst a high dose given in conjunction with vasopressin resulted in a diminution of the response below that found with the same concentration of vasopressin alone. Anterior pituitaries from vasopressin-deficient Brattleboro rats also show a phosphatidylinositol response to vasopressin. Pituitaries from rats that had been adrenalectomized 4 days earlier showed no increase in inositol phosphate accumulation in response to vasopressin. Daily administration of dexamethasone (40 micrograms/day) reversed this effect of adrenalectomy. This reversal was not seen when dexamethasone (40 micrograms/ml) was added to the incubation medium of adrenalectomized rat pituitary quarters. These results confirm that the rat anterior pituitary contains functional vasopressin receptors capable of activating inositol phospholipid metabolism and that this biochemical response is modified by changes in the hypothalamo-pituitary-adrenal axis.

Adrenalectomy↗

PubMed1987

Neonatal administration of a specific neuropeptide Y antiserum alters the vasopressin response to haemorrhage and the hypothalamic content of noradrenaline in rats.

The possibility that neuropeptide Y (NPY) exerts organizational effects on central noradrenergic systems was investigated by treating newborn rats with subcutaneous injections of a specific NPY-antiserum. Three months later, neuroendocrine function was determined by measuring plasma vasopressin following haemorrhage, since this response is known to be regulated by ascending noradrenergic pathways. Basal mean arterial pressure, heart rate and plasma vasopressin were similar in both control (normal rabbit serum-treated) and NPY-antiserum-treated rats. Treatment with this antiserum resulted in an impaired vasopressin response to haemorrhage, although the haemodynamic changes observed after this hypovolaemic challenge were similar to control rats. NPY and noradrenaline content in the hypothalamus and brainstem were examined at the end of these experiments. NPY-like immunoreactivity was similar in both groups of animals. However, electrochemical detection of noradrenaline after HPLC revealed significantly higher levels in the hypothalamus, but not brainstem, of NPY-antiserum-treated rats. The presence of enduring changes in noradrenaline levels and neurohypophyseal function following neonatal treatment with NPY-antiserum suggests a role for NPY in postnatal organization of the rat hypothalamus.

Animals↗

PubMed1987

Oxytocin responses to stress in lactating and hyperprolactinaemic rats.

The plasma oxytocin (OT) response to acute stress was compared between virgin, lactating, and hyperprolactinaemic female rats. In virgin rats, brief immobilization was associated with a significant elevation of plasma OT to 24.7 +/- 3.7 pmol/l compared with 7.7 +/- 1.1 pmol/l in controls. In contrast, the stress response was absent in lactating (6 days post-partum) animals: control OT 9.4 +/- 2.2, immobilized OT 9.0 +/- 1.1 pmol/l. Hyperprolactinaemia produced by treatment with either dopamine antagonists (domperidone or haloperidol) or ovine prolactin was also associated with an impairment of the OT stress response in intact females, whereas domperidone treatment failed to modify the response in ovariectomized (OVX) rats. Following ovarian steroid replacement with oestradiol and progesterone, the inhibitory effect of domperidone was observed in OVX rats: control OT 11.1 +/- 2.5, immobilized OT 16.0 +/- 3.7 pmol/l. Treatment of OVX rats with oestradiol and progesterone, either separately or combined, did not modify the OT stress response. Plasma levels of vasopressin were not significantly modified in either control or immobilized rats of any experimental groups. The results indicate that hyperprolactinaemia may be a causative factor in the impairment of OT stress responses observed in lactating rats.

Animals↗

PubMed1987

Increased renal sensitivity to vasopressin in two patients with essential hypernatremia.

Patients with essential hypernatremia maintain urinary concentrating ability despite plasma hyperosmolality and low plasma vasopressin concentrations. We investigated renal sensitivity to ultralow dose vasopressin infusions in two patients with a syndrome of hypodipsia, hypernatremia with selective osmoreceptor dysfunction, early puberty, and aggressive behavior. The patients were water loaded until a hypotonic diuresis was established. Vasopressin was infused in stepwise increments from 0.4-12 fmol/kg X min. Both patients had increased renal sensitivity to vasopressin, achieving negative free water clearance at infusion rates of 0.4 and 4 fmol/kg X min (normal greater than or equal to 6). Treatment for 3 months with 1-desamino-8-D-arginine vasopressin (DDAVP) led to an improvement in behavior and the reporting, for the first time, of a sensation of thirst. After DDAVP therapy both patients had a reduction of their renal sensitivity to infused vasopressin. We conclude that untreated patients with essential hypernatremia have increased renal sensitivity to vasopressin which is reduced by DDAVP administration.

Adolescent↗

PubMed1987

Changes in oxytocin and vasopressin secretion during sexual activity in men.

We measured plasma oxytocin (OT) and arginine vasopressin (AVP) concentrations in 13 normal men during sexual arousal and ejaculation. Mean plasma AVP increased from 1.4 +/- 0.2 (+/- SE) to 5.3 +/- 1.7 pmol/L (P less than 0.05) during arousal, but there was no significant change in OT. In contrast, at ejaculation mean plasma OT rose from a basal value of 1.4 +/- 0.3 to 7.3 +/- 0.6 pmol/L (P less than 0.01) and then fell to basal concentrations in 30 min. AVP, however, had returned to basal levels at the time of ejaculation and remained stable thereafter. We conclude that in man AVP is secreted during sexual arousal, and there is, subsequently, a selective release of OT at the time of ejaculation.

Adult↗

PubMed1987

Atrial natriuretic factor inhibits the stimulated in-vivo and in-vitro release of vasopressin and oxytocin in the rat.

The effect of an atrial natriuretic peptide on the secretion of the neurohypophysial peptides arginine vasopressin (AVP) and oxytocin has been studied in vivo and in vitro. Atriopeptin III was administered intracerebroventricularly to conscious rats and plasma concentrations of AVP and oxytocin were determined both in controls and in rats which had their drinking water replaced by 2% NaCl. The release of both AVP and oxytocin was inhibited when basal levels were increased by the saline treatment. The inhibition of AVP release lasted for 40 min whereas oxytocin release was inhibited for 10 min only. In a further experiment the stimulated release of AVP and oxytocin from the isolated neurointermediate lobe of the rat was also inhibited by atriopeptin III.

Animals↗

PubMed1987

Hypothalamo-hypophysial blood flow: a novel control mechanism in pituitary function?

The flow rate of portal plasma was measured during hypothalamo-hypophysial portal sampling in the rat using a modified Worthington-Fink technique. In rats rendered hypothyroid with propylthiouracil, there was a significant 140% increase in portal plasma flow. Median eminence stimulation also increased portal plasma flow by 41%. Orchidectomy and adrenalectomy had no effects on plasma flow. Modification of flow rate in the hypothalamo-hypophysial vascular bed may represent a further mechanism involved in the control of pituitary function.

Adrenalectomy↗

PubMed1987

Diurnal rhythm of vasopressin but not of oxytocin in the cerebrospinal fluid of the goat: lack of association with plasma cortisol rhythm.

Diurnal rhythms in the concentrations of vasopressin (AVP) and oxytocin in cerebrospinal fluid (CSF) differ between species and are unrelated to changes in the levels of these hormones in the peripheral circulation. We have investigated neurohypophysial hormone rhythms in the CSF of the conscious goat by determining whether they are entrained by daily cycles of light and darkness and by assessing the effect of the suppression of plasma cortisol. Goats were implanted with cisternal cannulae under halothane anaesthesia and allowed to recover. They were accustomed to a 12 h light:12 h darkness lighting cycle (lights on from 07.30 to 19.30 h). After initial serial CSF and plasma sampling the daily cycle of light and darkness was reversed. Three goats were kept in constant light for 8 days before the study and five were given dexamethasone (5 mg/12 h) for 4 days. There was a significant (P less than 0.01) diurnal variation in CSF concentrations of AVP, with a maximum of 3.6 +/- 0.8 (S.E.M.) pmol/l at 12.00 h and a minimum of 1.4 +/- 0.3 pmol/l at 24.00 h. There were no significant changes in CSF concentrations of oxytocin or plasma AVP. After the light:darkness cycle was reversed the AVP rhythm in the CSF was disrupted after 24 h and reversed after 8 days. The diurnal rhythm of AVP in CSF persisted in animals exposed to constant light. After treatment with dexamethasone plasma cortisol was suppressed and showed no diurnal rhythm but the AVP rhythm in CSF remained unchanged.

Animals↗

PubMed1987

Effect of naloxone on oxytocin and vasopressin release during vaginocervical stimulation in the goat.

We have investigated the secretion of oxytocin and arginine vasopressin (AVP) during vaginocervical stimulation in the conscious goat and examined the effect of the opioid antagonist naloxone on peptide release to this stimulus. Goats were implanted with guide tubes overlying the cisterna magna under anaesthesia and allowed to recover. Vaginocervical stimulation for 60 s resulted in a marked (P less than 0.01) release of oxytocin into the plasma but neither plasma AVP nor cerebrospinal fluid (CSF) concentrations of oxytocin changed significantly. In a second series of experiments, unoperated goats were infused with saline or naloxone (4 mg bolus + 12 mg/h) in random order on two separate occasions. Infusion of naloxone had no effect on basal plasma concentrations of oxytocin or AVP. There was a marked and significant (P less than 0.01) potentiation of oxytocin secretion following vaginocervical stimulation in animals infused with naloxone. Naloxone-infused animals showed a significant (P less than 0.01) rise in plasma AVP after stimulation but plasma AVP did not change in the saline-infused controls. We conclude that vaginocervical stimulation leads to the selective release of oxytocin from the neurohypophysis without affecting concentrations of oxytocin in the CSF. Endogenous opioids inhibit the stimulated secretion of oxytocin and AVP in vivo in response to vaginocervical stimulation in the goat.

Animals↗

PubMed1987

Quantitative measurements of retinal edema by specific gravity determinations.

We have quantified retinal edema in rat by specific gravity measurements in vitro. Specific gravity corresponds to tissue water content, which is increased in retinal edema. The gravimetric analysis of retinal edema corresponds well with light and transmission electron microscopy and radiolabelled albumen studies. Specific gravity measurements are the standard method to measure brain edema and are also applicable to the measurement of retinal edema.

Animals↗

PubMed1986

Diurnal pattern of stress-evoked neurohypophyseal hormone secretion: sexual dimorphism in rats.

Levels of oxytocin (OT) and arginine-vasopressin (AVP) in plasma of control or immobilized male and female rats were determined at various times of the day. Control levels of the neurohypophyseal peptides did not exhibit diurnal variation. Raised plasma levels of OT were found following immobilization at all times in both males and females, and a significant diurnal variation in stressed levels of OT was also observed, but in male rats only. Thus the morning stress responses (07.00 and 09.00 h) of males were markedly greater than the midday and evening responses, whereas the responses of females were similar throughout the day. A similar pattern was evident for AVP although plasma levels of AVP were not consistently elevated by stress. These findings provide further evidence of sexual dimorphism in both the regulation of neurohypophyseal stress responses and the periodicity of diurnal rhythms.

Animals↗

PubMed1986

Pressor effect of centrally administered neuropeptide Y in rats: role of sympathetic nervous system and vasopressin.

The haemodynamic effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) in urethane-anaesthetized rats were studied. In Sprague-Dawley rats, NPY increased both blood pressure and heart rate in a dose-dependent manner. This response was unaffected by removal of the adrenal medullae or pretreatment with a specific vasopressin antagonist (180 ng/kg i.v.), but was abolished by phenoxybenzamine (1mg/kg i.v.). After pretreatment with propranolol (1mg/kg i.v.), the tachycardia was inhibited and the pressor response was of shorter duration than in controls. In 6-hydroxydopamine treated rats (two doses of 250 micrograms i.c.v., three days apart), NPY still elicited a pressor response and tachycardia, which were significantly higher than controls 15 minutes after the injection. Plasma levels of vasopressin were not altered by i.c.v. administration of NPY. However, in Brattleboro rats the peptide had no haemodynamic effects. Our results suggest that activation of sympathetic nervous system but not release of vasopressin or adrenal catecholamines into the bloodstream mediates the cardiovascular response to NPY. Central vasopressin pathways however may be involved.

Animals↗

PubMed1986

Oxytocin release during coitus in male and female rabbits: effect of opiate receptor blockade with naloxone.

Blood was collected from freely moving rabbits pretreated with saline or naloxone both before and after coitus. In the males, ejaculation was associated with a marked increase in plasma oxytocin concentrations. In the females, oxytocin release was an all-or-nothing phenomenon-either there was no change in oxytocin or it rose to levels very similar to that found post-ejaculation in the males. Naloxone did not alter the proportion of occasions in which females showed an oxytocin response, nor did it have a significant effect on the levels of oxytocin achieved during coitus in either the male or the female rabbits.

Animals↗

PubMed1986

No effect of naloxone on plasma oxytocin in normal men.

The role of endogenous opiates in the control of the secretion of oxytocin in the basal state in healthy male volunteers was investigated with the opiate antagonist naloxone. There was no change in plasma oxytocin levels, assessed for a 120 min period following the intravenous administration of naloxone (10 mg). Although there was no effect of opiate receptor blockade with naloxone in this basal situation, further studies are needed to evaluate the possible role of opioid regulation of oxytocin during lactation and parturition.

Adult↗

PubMed1986

The effect of indomethacin on the renal response to arginine vasopressin in man.

The renal response to graded intravenous infusions of arginine vasopressin (AVP) was investigated in a two part study in six volunteers. First, under maximal water diuresis, seven control incremental infusions of AVP were given from zero to 12 fmol min-1 kg-1. Second, the AVP infusions were repeated after pretreatment with indomethacin, 150 mg daily for 36 h. After the AVP infusions, plasma AVP concentrations did not change significantly and remained within the physiological range; in contrast, urinary AVP excretion rate increased steadily. Indomethacin did not alter the plasma or urinary concentrations of AVP. AVP caused a fall in urine flow rate from a state of maximal diuresis to one of maximal antidiuresis. After indomethacin, fractional free water clearance was reduced by an average of 26% at the zero, 2 and 4 fmol min-1 kg-1 infusion rates of AVP. A significant increase in fractional sodium clearance of approximately 50% occurred during the AVP infusions, which was abolished after pretreatment with indomethacin. After indomethacin, urinary prostaglandin E2 (PGE2) excretion rate was reduced by an average of 40% at the zero and 2 fmol min-1 kg-1 infusion rates of AVP. At higher AVP infusion rates, no significant inhibition of PGE2 was observed. Urinary kallikrein excretion rate decreased steadily to one-third of its original value after AVP and this change remained unaltered by indomethacin. The findings show that infusions of AVP, resulting in plasma concentrations in the physiological range, evoke a maximal antidiuretic response, which is accompanied by natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Pressor effect of arginine vasopressin in progressive autonomic failure.

The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers. Stepwise infusion of NA at rates of 300-3000 pmol min-1 kg-1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60-300 pmol min-1 kg-1. Stepwise infusion of AVP at 0.2-5.0 pmol min-1 kg-1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000-4000 pmol/l, and still no significant pressor response was observed. Stepwise infusion of AVP at 0.05-2.0 pmol min-1 kg-1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 +/- 0.2 (mean +/- SEM) to 30 +/- 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 +/- 1.8 pmol/l.

Adult↗

PubMed1986

Hormonal and cardiovascular responses to DDAVP in man.

Hormonal and cardiovascular responses to 1-desamino-8-D-arginine vasopressin (DDAVP) were investigated in six normal adult volunteers. After overnight fluid deprivation, an intravenous injection of either DDAVP (0.4 microgram/kg) or the same volume of normal saline was administered. One hour later an intravenous infusion of hypertonic saline was commenced and continued over two hours. Five minutes following the DDAVP injection, facial flushing, a fall in diastolic blood pressure by an average of 13% and a rise in pulse rate by an average of 18% were observed. There was a significant increase in plasma renin activity and plasma cortisol concentration, but no significant changes were observed in plasma concentrations of LH, FSH, TSH, prolactin or GH. Following osmotic stimulation by hypertonic saline plasma AVP rose to the same extent in both the DDAVP and control studies. DDAVP (0.4 microgram/kg) was also administered to five subjects with cranial diabetes insipidus. Again facial flushing, increased facial temperature, a fall in diastolic pressure and a rise in heart rate were all observed, suggesting that DDAVP exerts its cardiovascular actions by a mechanism other than antagonism of circulating endogenous AVP.

Adult↗

PubMed1986

Oral hypertonic saline causes transient fall of vasopressin in humans.

After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l (P less than 0.05) 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l (P less than 0.05) after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration.

Administration, Oral↗