PubMed Health⌕ Search

Biomedical subjects

S L Lightman

Publications and source records attributed to S L Lightman.

At least 397 records · Page 22Linked to original sources
PubMed1986

Antidiuretic effect and pharmacokinetics of oral 1-desamino-8-D-arginine vasopressin. 1. Studies in adults and children.

The dose-response relationships and pharmacokinetics of orally administered 1-desamino-8-D-AVP (DDAVP) were investigated. In water-loaded normal subjects marked reductions in urine flow rate and increases in urinary osmolality occurred. The responses were maximal 2 h after ingestion of 50, 100, and 200 micrograms, and lasted at least 6 h. Plasma DDAVP levels increased in a dose-dependent fashion and its disappearance from the plasma followed an exponential time course, with a half-life 86 to 142 min. In water-loaded adults with central diabetes insipidus (CDI), 200 micrograms oral DDAVP caused marked antidiuresis and mean urinary osmolality increased from 107 mosm/kg to 554 mosm/kg after 3 h. In these patients the effect also lasted at least 6 h. Children with CDI were less sensitive than normal subjects to the 50-microgram dosage and required 100 micrograms orally to achieve a duration of action similar to that resulting from 200 micrograms in adults. Oral DDAVP may be useful for treating some patients with CDI.

Administration, Intranasal↗
PubMed1986

Vasopressin and oxytocin responses to acute and chronic osmotic stimuli in man.

The regulation of both arginine vasopressin (AVP) and oxytocin secretion was studied during rapid and prolonged osmotic stimuli in normal adult volunteers. In five subjects given an intravenous infusion of 0.85 mol NaCl at 0.05 ml/kg per min over 2 h there was a significant (P less than 0.05) rise only in plasma AVP, with no significant change in plasma levels of oxytocin. In six further subjects 5 days of restriction to 500 ml fluid daily resulted in significant increases of both plasma and 24-h urinary AVP, whereas there was no change in corresponding oxytocin levels. During another 5-day period in which the same subjects were given an additional 200 mmol sodium as well as having their fluid intake restricted to 1000 ml daily, there were again significant rises in plasma and 24 h urinary AVP with no change in corresponding oxytocin levels. We conclude that, in man, AVP is selectively secreted in response to both dehydration and high sodium intake, whilst even after the stimulus of rapidly increasing plasma osmolality during intravenous infusion of hypertonic saline the rise in oxytocin is not statistically significant. It therefore appears unlikely that oxytocin has a significant role in the physiological control of fluid balance in man.

Adult↗
PubMed1986

A sex difference in endogenous opioid regulation of the posterior pituitary response to stress in the rat.

The influence of endogenous opioids on the posterior pituitary response to stress was investigated by measuring plasma hormone levels in immobilized male and female rats following either acute naloxone treatment or prolonged morphine administration. Naloxone significantly potentiated the oxytocin and arginine vasopressin (AVP) response to immobilization, but in female rats only. The responses of morphine-treated male rats showed differences compared with vehicle-treated controls, although chronic morphine treatment did not reliably alter the oxytocin or AVP responses to immobilization in males or females. In a further experiment to investigate the role of gonadal hormones in determining the sex difference in responsiveness to naloxone, it was found that acute naloxone treatment significantly potentiated the posterior pituitary response to stress in castrated male rats. These results extend previous studies showing a sex difference in stress-induced secretion of posterior pituitary hormones, providing evidence of a sexual dimorphism in the endogenous opioid regulation of this response which is partly determined by circulating gonadal hormones.

Animals↗
PubMed1986

The effect of SMS 201-995, a long-acting somatostatin analogue, on anterior pituitary function in healthy male volunteers.

The endocrine effect of SMS 201-995, an octapeptide analogue of somatostatin, was assessed during a combined anterior pituitary function test. There was no effect on the extent of hypoglycaemia after intravenous insulin infusion or on the subsequent rate of recovery of plasma glucose. SMS 201-995 administration, however, resulted in a profound and selective suppression of the GH response to hypoglycaemia without affecting the ACTH or cortisol responses. There was also a marked reduction of TSH release in response to intravenous TRH; the prolactin response was unimpaired. The LH response to LHRH was blunted and the FSH response unaffected. SMS 201-995 does not significantly impair the counterregulatory mechanisms in response to hypoglycaemia, and, in particular, the hypothalamic-pituitary-adrenal axis remains intact.

Adrenocorticotropic Hormone↗
PubMed1985

Neurotensin-like immunoreactivity and neurotensin receptors in the rat hypothalamus and in the neurointermediate lobe of the pituitary gland.

In the rat hypothalamus, cell bodies containing neurotensin-like immunoreactivity were mainly found in the medial preoptic area, the periventricular nucleus, the paraventricular nucleus, the supraoptic nucleus and the arcuate nucleus. [3H]neurotensin binding sites were observed throughout the hypothalamus with a dense accumulation of silver grains over the paraventricular nucleus, the arcuate nucleus and the median eminence region. By radioimmunoassay neurotensin-like immunoreactivity was also found in the neurointermediate lobe of the pituitary gland of various mammalian species and in human postmortem posterior pituitary glands. In the rat studies involving pituitary stalk transections and the neurotoxin monosodium glutamate indicated the presence of a neurotensinergic pathway from the arcuate nucleus to the neurointermediate lobe of the pituitary gland. [3H]neurotensin binding sites were found to be concentrated over the intermediate lobe of the pituitary gland and their presence was not affected by pituitary stalk transection, indicating their localization on endocrine cells of the intermediate lobe of the pituitary gland.

Animals↗
PubMed1985

Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma.

Safety and efficacy of a slow-release formulation of D-Trp-6-luteinising-hormone-releasing-hormone (D-Trp-6-LHRH) microcapsules were compared with orchidectomy in the initial treatment of advanced prostatic carcinoma. 41 patients were randomly assigned to D-Trp-6-LHRH and 38 to orchidectomy. Suppression of testosterone and reduction in prostatic acid phosphatase levels were similar in both groups. 87% of patients in the D-Trp-6-LHRH group and 81% in the orchidectomy group responded to treatment or showed no deterioration. Side-effects related to the decrease in testosterone were similar in both groups. 3 patients given D-Trp-6-LHRH had a disease "flare" in the first ten days of treatment which resolved completely when testosterone fell to castrate levels. Results of psychological assessment were similar in both groups before treatment, and on follow-up there was a weak trend towards decreased psychological morbidity in the hormone group. The slow-release preparation of D-Trp-6-LHRH microcapsules offers an important alternative in the management of advanced prostatic carcinoma.

Aged↗
PubMed1985

Cardio-respiratory actions of substance P, TRH and 5-HT in the nucleus tractus solitarius of rats: evidence for functional interactions of neuropeptides and amine neurotransmitters.

The cardiovascular and respiratory effects of Substance P (SP) and Thyrotrophin-Releasing Hormone (TRH) microinjections into the nucleus tractus solitarius (NTS) of urethane anaesthetized rats have been investigated. Dual injections of the peptides with serotonin (5-HT) were given to investigate possible functional interactions. In addition, SP and TRH were injected into rats in which 5-HT in the NTS area had been depleted by prior treatment with 5,7-Dihydroxytryptamine (5,7-DHT). SP (65pmol) did not elicit significant effects on blood pressure (BP) or heart rate (HR), but produced a marked, acute reduction in respiration rate (RR). TRH (110pmol) elicited a small but significant reduction in mean arterial pressure (MAP), whereas 5-HT (15nmol) caused a rise in MAP. Neither TRH nor 5-HT modified RR when given alone. A dual injection of SP (6.5pmol, ineffective alone) and 5-HT (15nmol) resulted in a rise in MAP which was insignificantly different from the effect of 5-HT alone. However, a prolonged fall in RR, unlike the effect of SP alone was also observed. A dual injection of TRH (11pmol, ineffective alone) and 5-HT (15nmol) resulted in a profound fall of RR but no significant changes in MAP or HR. SP elicited similar effects in 5,7-DHT lesioned animals as in sham operated controls. In contrast, TRH microinjections in lesioned rats were associated with a profound fall in RR, and a blood pressure response significantly different to that observed in the corresponding sham group. The results are discussed in relation to other evidence suggesting functional interactions between neuropeptides and amine neurotransmitters in the mammalian brainstem.

5,7-Dihydroxytryptamine↗
PubMed1985

Influence of endogenous and exogenous oestrogens on posterior pituitary secretion in women.

Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d.

Adult↗
PubMed1985

Selective cardiovascular and neuroendocrine effects of a kappa-opioid agonist in the nucleus tractus solitarii of rats.

The cardiovascular and neuroendocrine effects of a selective kappa-opiate receptor agonist (U50488H) microinjected into the nucleus tractus solitarii have been investigated in urethane-anaesthetized rats. Comparative experiments were conducted using 8-arginine vasopressin (AVP)-deficient Brattleboro rats and an opiate agonist selective for delta receptors. Unilateral injection of U50488H elicited a significant dose-dependent increase in mean arterial pressure and a small decrease in heart rate in Sprague-Dawley rats. The pressor effect was blocked preferentially by the relatively selective kappa-receptor antagonist MR2266BS compared to naloxone. Bilateral injections of U50488H elicited a relatively greater increase in mean arterial pressure than unilateral injections and a significant decrease in heart rate. U50488H did not elicit a pressor effect in Brattleboro rats, whereas a marked response (associated with a significant increase in AVP secretion) was found in parent strain Long-Evans rats. In contrast, no such differential effects in the response of Brattleboro and Long-Evans rats were observed in parallel experiments using equimolar doses of the selective delta-opiate agonist Tyr-D-Ser-Gly-Phe-Leu-Thr which elicited a transient pressor response. An antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid)2-(0-methyl) tyrosine] arginine vasopressin (1,d(CH2)5Tyr(ME)AVP) specific for the vasopressor action of AVP blocked the U50488H-induced pressor response in a dose-dependent manner when administered intravenously 10 min prior to the kappa agonist, but did not significantly attenuate the response to the delta agonist. Conversely, the U50488H-induced response was not modified by pre-treatment with phenoxybenzamine whereas the delta-agonist pressor response was completely blocked by it. The results provide evidence for specific kappa-opiate cardiovascular and neuroendocrine responses in the nucleus tractus solitarii and suggest that a kappa-receptor mechanism, possibly involving a peptide of the dynorphin group as the endogenous ligand, may operate in the central control of blood pressure and AVP secretion.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1985

Vasopressin secretion in progressive autonomic failure: evidence for defective afferent cardiovascular pathways.

Patients with progressive autonomic failure with multiple system atrophy show a severely blunted response of plasma arginine vasopressin to the stimulus of head-up tilt. Whether this could be due to lesions either at one or more sites within ascending neural pathways from cardiovascular stretch receptors in the thorax or, alternatively, to lesions affecting vasopressin secreting cells within the hypothalamus was investigated. The arginine vasopressin response to an intravenous infusion of hypertonic saline was determined in six patients with progressive autonomic failure. The mean plasma concentration of arginine vasopressin rose from 1.0 to 3.7 pmol/l, a change comparable to that observed in normal controls. This demonstrates normal functioning of the efferent connections from the osmoreceptors within the hypothalamus and suggests that the loss of vasopressin response to head-up tilt is due to lesions in ascending pathways from cardiovascular receptors. There was a significant rise in mean blood pressure during the infusions on patients with progressive autonomic failure, a change which was not observed with the controls. This may have been at least partly caused by the rise in circulating arginine vasopressin concentrations, since these patients have been reported to be extremely sensitive to the pressor effects of arginine vasopressin.

Afferent Pathways↗
PubMed1985

Sexual dimorphism in the posterior pituitary response to stress in the rat.

The posterior pituitary response to immobilization was studied in male and female rats. Plasma levels of arginine vasopressin (AVP) and oxytocin (OT) were measured both in control rats and in rats immobilized in an acrylic restrainer for 1 min. In male rats immobilization did not result in any change in AVP (control: 1.3 +/- 0.2 pmol/liter, mean +/- SEM; immobilized: 2.3 +/- 0.6 pmol/liter), although there was a small but significant increase in OT (control; 4.1 +/- 0.5 pmol/liter; immobilized: 10.2 +/- 2.2 pmol/liter; P less than 0.005). In female rats a marked rise was observed in AVP (control: 1.4 +/- 0.3 pmol/liter; immobilized: 5.5 +/- 1.3 pmol/liter; P less than 0.005), and the rise in OT was considerably greater (P less than 0.01) than that found in males (control: 4.7 +/- 0.8 pmol/liter; immobilized: 26.0 +/- 5.6 pmol/liter; P less than 0.001). Further groups of male and female rats were gonadectomized 2 weeks before immobilization. Basal levels of AVP and OT were unchanged. Orchidectomized males had an increased OT response to immobilization compared with sham-operated males (P less than 0.05) whereas the AVP response was not significantly changed. Ovariectomy did not significantly affect either the AVP or OT responses. Although the neural pathways responsible for the neurohypophyseal response to immobilization are not known, this data demonstrate that the response is dependent on the sex of the rat.

Animals↗
PubMed1985

Circadian rhythms of epinephrine and norepinephrine in man.

The diurnal rhythms of plasma epinephrine and norepinephrine were investigated in a group of normal young men. Sleep, posture, illumination, and food intake were monitored. Plasma epinephrine demonstrated a statistically significant diurnal rhythm, with a mean amplitude of 14 +/- 1.6 (+/- SE) pg/ml superimposed on a mean level of 43 +/- 5.3 pg/ml. The trough occurred at 03.20 h +/- 35 min. Plasma norepinephrine had a significant diurnal rhythm, with a mean amplitude of 111 +/- 19 pg/ml superimposed on a mean level of 413 +/- 25 pg/ml, with the trough occurring at 02.20 h +/- 30 min. There was a significant correlation between the two rhythms at zero phase shift, with a pooled value for the group of r = 0.49. Epinephrine levels had no direct relationship to sleep or posture, whereas norepinephrine levels were significantly higher with upright posture and higher when the men were awake than when asleep. Our results indicate that circadian variations in the sympathetic-adrenal medullary system are not explained by a single controlling influence and that the norepinephrine rhythm can be accounted for as a direct response to changes in posture and sleep, whereas the epinephrine rhythm is probably controlled by a circadian oscillator.

Blood Specimen Collection↗
PubMed1985

Oxytocin and sexual behaviour in the male rat and rabbit.

In male New Zealand white rabbits, it was shown that oxytocin but not vasopressin concentrations in plasma were markedly raised after ejaculation. In male Wistar rats, oxytocin infused into the internal carotid artery reduced the number of intromissions made before ejaculation but had no other significant effect. Infusion of oxytocin into the third ventricle increased the latencies to the first mount and intromission and lengthened post-ejaculatory refractory periods. It is suggested that oxytocin released into the periphery during coitus, while not essentially involved in ejaculation, may exert effects on the genital periphery. Behavioural effects of centrally administered oxytocin suggest that it may play a role in the neural mechanisms underlying post-ejaculatory refractoriness.

Animals↗
PubMed1984

Haemodynamic effects of arginine-vasopressin microinjections into the nucleus tractus solitarius: a comparative study of vasopressin, a selective vasopressin receptor agonist and antagonist, and oxytocin.

Arginine-vasopressin (AVP) and related peptides were administered by microinjection into the nucleus tractus solitarius of the rat. AVP produced a rise both in mean arterial pressure and in heart rate. This effect was abolished by pretreatment with a specific antagonist of V1 receptors and was not seen either after injections of oxytocin or of the V2 agonist deamino-D-arginine-vasopressin. This study provides evidence for a specific action of vasopressin on the cardiovascular system in the nucleus of the tractus solitarius, which is mediated neither by V2 nor oxytocin receptors.

Animals↗
PubMed1984

Neurotensin in the rat anterior pituitary gland: effects of endocrinological manipulations.

Neurotensin-like immunoreactivity was detected by radioimmunoassay in the anterior lobe of the pituitary gland of several mammalian species, including man. In the rat, pituitary stalk transection did not change the content of neurotensin-like immunoreactivity. Surgical and chemical thyroidectomy produced a drastic reduction of neurotensin-like immunoreactivity in the anterior pituitary gland, whereas adrenalectomy and gonadectomy were without an effect and the decrease consequent to thyroidectomy was restricted to the pituitary gland. These results suggest an interaction between neurotensin and the hypothalamus/pituitary/thyroid axis at the level of the anterior pituitary gland.

Adrenal Glands↗
PubMed1984

Ascending noradrenergic projections from the brainstem: evidence for a major role in the regulation of blood pressure and vasopressin secretion.

The role of projections from the lateral tegmental (A1, A2) and coeruleal (A6) noradrenergic cell groups in the control of arginine vasopressin (AVP) secretion was studied following lesions to the ventral (VNAB) and dorsal (DNAB) noradrenergic bundles by 6-hydroxydopamine. These lesions were associated with the expected, large reductions in cortical (DNAB) and hypothalamic (VNAB) noradrenaline concentrations. Vehicle injected, control animals and VNAB lesioned animals showed a similar AVP secretory response to haemorrhage, whilst the DNAB group showed a markedly diminished release of AVP in response to this challenge. Following Clonidine injection, both controls and VNAB animals showed major reductions in plasma AVP concentrations, but again the DNAB group behaved in a different manner, with a marked attenuation of the inhibitory effect of Clonidine on AVP secretion. In addition, the DNAB group had a significantly lower basal blood pressure, a greater initial agonist response to Clonidine and a loss of the hypotensive response to Clonidine in comparison to sham and VNAB lesioned groups. All three groups showed a similar AVP response to intravenous nicotine. These data suggest that noradrenergic projections originating in the locus coeruleus, or in the lateral tegmental NA groups but which ascend together with coeruleal axons in the DNAB, modulate the vasopressin response to visceral stimuli and to Clonidine, and that they also play an important role in mediating the hypotensive effect of Clonidine.

Afferent Pathways↗