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Biomedical subjects

D A Carter

Publications and source records attributed to D A Carter.

At least 127 records · Page 7Linked to original sources

A case of nasal glioma and neurofibromatosis. A new association.

A man of 25 with von Recklinghausen's neurofibromatosis (VR) developed nasal polyps. Subarachnoid haemorrhage occurred shortly after surgical excision and he died 9 weeks later. Post-mortem examination showed chronic hydrocephalus due to aqueduct stenosis. Histologically the polyps were a nasal glioma, a forme fruste of anterior encephalocoele not previously associated with VR, though other cranial defects are well recognized. Nasal glioma should be considered in the differential diagnosis of nasal lesions in VR.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Subdural meningioma of spinal cord. Case report.

A case of extensive circumferential meningioma of the spinal subdural space is reported. A potential mechanism for this growth pattern is proposed, and preoperative diagnosis by computerized tomography is discussed. This case reinforces the necessity for intradural exploration when an expected extradural neoplasm is not encountered at operation.

Adult↗

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↗

Evidence for an increased opioid inhibition of LH secretion in hyperprolactinaemic ovariectomized rats.

The effects of acute and sub-chronic hyperprolactinaemia on the positive feedback action of progesterone in oestrogen-primed ovariectomized rats have been compared. A single injection of ovine prolactin administered with progesterone had no effect on the LH surge measured 5 h later although hyperprolactinaemia induced by 5-day treatment with the dopamine antagonist, domperidone, markedly attenuated the surge. Repeated injections of naloxone (5 mg/kg) during the development of the progesterone-stimulated LH surge completely reversed this inhibitory effect of hyperprolactinaemia, but had no apparent effect on the positive feedback action in control animals. In oestrogen-primed animals similar treatment with naloxone (0.4 and 5 mg/kg) stimulated LH secretion but the increase was significantly smaller than that observed after injecting progesterone. It is suggested that hyperprolactinaemia increases the inhibitory opioid modulation of LH release and that this effect is responsible for the impairment of the positive feedback action of progesterone.

Animals↗

Substance P microinjections into the nucleus tractus solitarius elicit a pressor response in capsaicin-treated rats.

The role of Substance P in the nucleus tractus solitarius was investigated by observing the effect of local injections of the peptide on blood pressure, heart rate and vasopressin secretion in both normal and neonatally capsaicin-treated rats. Substance P did not modify and of these parameters in control rats, but elicited a marked pressor response, not associated with changes in heart rate or plasma vasopressin levels, in capsaicin-treated animals. The study demonstrates that neonatal capsaicin treatment modifies the sensitivity of this area of the brainstem to exogenous substance P and provides evidence for a modulatory action of substance P on the cardiovascular system at the site of the nucleus tractus solitarius.

Afferent Pathways↗

Progesterone administration prolongs the inhibitory effects of hyperprolactinemia on luteinizing hormone secretion in acutely ovariectomized rats.

Several studies have shown that hyperprolactinemia in rats inhibits the post-gonadectomy rise in plasma luteinizing hormone (LH) for a limited period only. In intact rats the suppression of plasma LH during hyperprolactinemia is more prolonged. In the present study we have examined the possibility that the elevated levels of progesterone brought about by the raised plasma prolactin levels in intact rats are involved in the maintenance of LH inhibition. We have observed the effect of exogenous progesterone administration during the early post-ovariectomy period on plasma LH levels in female rats made hyperprolactinemic by administration of the dopamine antagonist, domperidone. Following ovariectomy of virgin, female rats, plasma LH was determined on each day from Day 3 to Day 10 after ovariectomy. In control rats plasma LH had increased by approximately 5-fold during the period of the experiment. In control rats treated with progesterone the rise in plasma LH was inhibited temporarily but LH had increased to similar levels to the controls by Day 10. In hyperprolactinemic rats LH was suppressed until Day 7, after which significant rises were observed. However, in hyperprolactinemic rats treated with progesterone, LH did not rise in a similar fashion, and remained low throughout the experiment. We conclude that a combination of hyperprolactinemia and raised plasma progesterone concentrations is necessary for the continued inhibition of LH release after ovariectomy.

Animals↗

Characterization of the inhibitory effects of hyperprolactinaemia on the mechanism controlling LH secretion in chronically ovariectomized rats.

The time-course of the inhibitory effect of hyperprolactinaemia on LH secretion was delineated. Hyperprolactinaemia was induced in ovariectomized rats with injections of domperidone or ovine prolactin and circulating LH levels were measured from 1 h to 9 days after the treatment. Inhibition of LH secretion occurred within 2-4 h after treatment, and was maintained (provided that serum prolactin remained elevated) for a period of 6 days only. Thereafter LH levels increased to become insignificantly different from control levels on Day 9. A reduction in pituitary responsiveness was not associated with the acute or sub-chronic inhibition of LH secretion, although a significant fall in responsiveness was observed simultaneously with the return of serum LH levels to control values. No changes in hypothalamic LH-RH content was found. It is concluded that an impairment of pituitary function is not responsible for the inhibitory action of prolactin on LH secretion.

Animals↗

The effect of chronic neuroleptic treatment on gonadotrophin release.

Although neuroleptic-induced hyperprolactinaemia is a common cause of amenorrhoea in women, the mechanism by which ovarian function is disturbed is unknown. Previous studies on both hyperprolactinaemic women and rats have indicated that an impairment of the pituitary response to LH-RH may be involved. We have investigated this possibility in female psychiatric patients undergoing chronic treatment with depot neuroleptics. The patients and a group of healthy controls were subjected to a standard LH-RH provocation test. Basal and post-stimulation serum levels of gonadotrophins, prolactin and oestradiol were determined. We have found that the LH responses of the patients fell into three groups: exaggerated, normal and impaired. Differences in the basal levels of gonadotrophins were also observed. The abnormal basal hormone levels and LH-RH responses appear to be related to neuroleptic dose and/or serum prolactin concentration, but no well-defined relationship was found. The results suggest that an action of the neuroleptics which is independent of high serum prolactin levels may be involved in the disruption of pituitary function. Thus the amenorrhoea caused by neuroleptic drug treatment may be etiologically different from that of other forms of hyperprolactinaemic amenorrhoea.

Adult↗

In-vivo and in-vitro effects of domperidone on the release of prolactin and LH in male and female rats.

Domperidone at a dose of 4 mg/kg significantly raised circulating prolactin levels in male and female rats although this increase was approximately 4-fold higher in females compared with males. No effect on LH secretion was observed. This LH and prolactin responses to Gn-RH and TRH respectively were investigated with isolated perfused pituitary glands obtained from domperidone-pretreated animals. For females, the basal release of prolactin was raised by domperidone pretreatment and the responsiveness of the pituitary to Gn-RH was markedly attenuated. When domperidone was added to the perfusing media, high concentrations (100 microgram/ml) reduced both the basal and TRH-stimulated prolactin secretion from pituitaries of untreated male and female rats although lower doses (1 microgram/ml and 10 ng/ml) were ineffective in altering prolactin release. The pituitary LH responses to Gn-RH were similarly reduced by the presence of 100 microgram domperidone/ml in the medium.

Animals↗

Dynamic changes in pituitary responses to luteinizing hormone releasing hormone after ovariectomy in the rat.

Changes in pituitary responses to pulses of LH releasing hormone (LH-RH) after ovariectomy in the rat have been investigated with an in-vitro perifusion system. On the third day after ovariectomy there was a large increase in the responsiveness of the pituitary gland to LH-RH compared with days 1 and 2 and this preceded the first significant rise in circulating concentrations of LH. Exaggerated responses were observed on all subsequent days tested (days 4, 6, 10, 18 and 28) although the size of the response on day 10 was significantly lower compared with days 6, 18 or 28. It is suggested that the early phase of increased pituitary responsiveness to LH-RH results from a rise in pituitary LH-RH receptors, which increases both the synthesis of LH and the response to exogenous LH-RH. The reduced LH response, measured on day 10, may correlate with an increase in the endogenous secretion of LH-RH and an imbalance between LH synthesis and secretion at this time.

Animals↗