Effect of dual chamber pacing on raised plasma atrial natriuretic peptide concentrations in complete atrioventricular block.
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Adult↗
Biomedical subjects
S L Lightman
Publications and source records attributed to S L Lightman.
Hypothalamo-hypophyseal portal blood sampling from laboratory rats. The effects of endocrine manipulations on portal blood catecholamine concentrations.
We have obtained hypothalamo-hypophyseal portal blood using a modified Worthington-Fink technique, and measured the concentrations of catecholamines with a high pressure liquid chromatography - electrochemical detection system. The concentrations of noradrenaline, adrenaline and dopamine have been measured in portal blood after various endocrine manipulations, including adrenalectomy, orchidectomy and chemically induced hypothyroidism. After the induction of hypothyroidism, dopamine concentrations in portal blood increased. After orchidectomy, there was an increase in portal adrenaline concentration, though noradrenaline and dopamine were unchanged.
Adrenalectomy↗
Rebound increase in plasma renin and vasopressin following graded infusions of atrial natriuretic peptide in man.
The effects of graded infusions of atrial natriuretic peptide (ANP) on hemodynamics, renal function, plasma renin activity (PRA) and plasma arginine vasopressin (AVP) were investigated in a two part study in 6 volunteers. Three 30-min iv infusions of either saline control or ANP at graded rates of 4, 10 and 40 pmol kg-1 min-1 were given. ANP infusions were associated with a significant increase in sodium clearance from 1.08 +/- 0.21 to 2.83 +/- 0.50 ml/min, an increase in hematocrit and a net fluid loss. Plasma AVP remained constant during ANP infusions but increased significantly afterwards when plasma ANP concentrations were falling rapidly, and this was accompanied by marked antidiuresis. PRA fell by 23% during the saline control infusions and by 50% during ANP infusions. Following cessation of ANP infusions there was a significant rebound increase in PRA. No changes were observed in blood pressure, heart rate, glomerular filtration rate or renal plasma flow. These results suggest an interaction in man between ANP and the hormones renin and AVP.
Adult↗
Decline of atrial natriuretic peptide release in dogs during sustained rapid cardiac pacing.
1. To assess the ability of the atria to maintain elevated plasma concentrations of atrial natriuretic peptide (ANP), the temporal changes in plasma ANP concentrations were studied in seven chloralose-anaesthetized dogs during 4 h of sustained rapid cardiac pacing. 2. Heart rate increased from 124 +/- 26 (mean +/- SEM) to 278 +/- 28 beats/min for the 4 h duration of rapid cardiac pacing. Mean pulmonary wedge pressure increased from 3.6 +/- 1.8 to 17.4 +/- 7.1 mmHg at 30 min (P less than 0.01) and mean right atrial pressure rose from -1.7 +/- 1.9 to 2.0 +/- 2.8 mmHg at 30 min (P less than 0.01). Both remained constant at these elevated pressures for the entire 240 min of rapid pacing. 3. Arterial ANP concentrations increased in all dogs from 87 +/- 11 to a maximum of 1263 +/- 592 pmol/l at 30 min (P less than 0.01), falling to 411 +/- 42 pmol/l after 60 min and to 146 +/- 70 pmol/l after 240 min of rapid continuous pacing (P less than 0.01 compared with 30 min). Coronary sinus ANP concentrations showed a similar pattern, rising from 241 +/- 79 to a maximum of 1837 +/- 203 pmol/l after 30 min (P less than 0.01). These peak values likewise were not sustained, falling to 962 +/- 198 pmol/l after 60 min and 297 +/- 41 pmol/l after 240 min of rapid pacing (P less than 0.01 compared with 30 min). 4. It is concluded that atria are unable to maintain the peak concentrations of ANP reached after 30 min of rapid pacing despite persistently elevated atrial pressures.
Animals↗
Atrial natriuretic peptide released by rapid ventricular pacing in dogs does not cause a natriuresis.
1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min. 2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P less than 0.05), and decreased cardiac output and mean arterial pressure (P less than 0.05). 3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P less than 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change significantly. 4. Urine flow and free water clearance increased during the latter 30 min of pacing (P less than 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP. 5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.
Animals↗
How would you like to have an orchidectomy for advanced prostatic cancer?
One hundred thirteen patients were randomized for the study. There was no significant difference between the groups for response or survival. The incidence of side effects related to the reduction of testosterone was similar in both groups. Disease "flare" was seen in three patients treated with long-acting D-Trp-6 LH-RH. All symptoms resolved by the end of 8 weeks. There was less psychological morbidity in the D-Trp-6 LH-RH group but the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6 LH-RH offers a safe and effective alternative to surgical orchidectomy.
Antineoplastic Agents↗
Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.
The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.
Adult↗
Increased sensitivity to pressor hormones in central diabetes insipidus.
Pressor sensitivities to infusions of arginine vasopressin (AVP), noradrenaline (NA) and angiotensin II (AII), as well as cardiovascular responses to head-up tilt, were assessed in subjects with central diabetes insipidus (CDI) and compared with those in normal control subjects. During incremental i.v. infusions of AVP at 0.2-5.0 pmol min-1 kg-1, mean arterial blood pressure (MABP) rose progressively in CDI subjects only and the rise was significantly greater than that which occurred in control subjects during their final infusion. The pressor effects of incremental i.v. infusions of NA and AII were greater, and the bradycardia associated with NA was more pronounced, in CDI subjects than in controls. Whole body tilt from supine to 45 degrees head-up was associated with increased heart rate and an insignificant rise in MABP in both groups, although a rise in plasma AVP occurred in control subjects only. These results demonstrate that subjects with CDI are more sensitive than control subjects to the pressor effects of NA and AII, and also develop sensitivity to the pressor effects of AVP. Their cardiovascular responses to head-up tilt remain intact. Presumably the increased vascular sensitivity to NA and AII in subjects with CDI is sufficient to compensate for their lack of AVP response during head-up tilt.
Adult↗
The TSH, T4, T3 and prolactin responses to consecutive infusions of a potent and stabilized thyrotrophin releasing hormone analogue, RX77368, in man.
The endocrine manifestations of a stabilized thyrotrophin releasing hormone (TRH) analogue, RX77368, have been investigated in six male volunteers. Infusions were given on two occasions, with a 5-day interval between infusions. On the second exposure to RX77368, there was a significant reduction in the TSH response, despite normal basal T3 and T4 levels, while the response of prolactin to RX77368 was unaltered. Domperidone administered during the infusion of RX77368 caused a further elevation of prolactin levels, whilst TSH levels were unchanged. This study shows the differential regulation of thyrotrophs and lactotrophs in response to stimulation by a TRH analogue, and shows, for the first time, down-regulation of the TSH response in vivo, in the presence of normal peripheral thyroid hormone levels. The T3 response to infusions of RX77368 was less than to a bolus injection of TRH, despite a greater TSH response to the analogue, suggesting impaired biological activity of TSH released in response to an infusion of the analogue.
Adult↗
Corticotrophin-releasing factor, vasopressin and pro-opiomelanocortin mRNA responses to stress and opiates in the rat.
1. Rats underwent either: (1) acute or chronic morphine or naloxone administration; (2) simple morphine withdrawal or naloxone-precipitated withdrawal in morphine-dependent animals; or (3) stress from I.P. administration of hypertonic saline. 2. Quantitative in situ hybridization histochemistry was performed using synthetic oligonucleotide probes for corticotrophin-releasing factor (CRF), vasopressin, pro-opiomelanocortin (POMC), dynorphin, enkephalin and oxytocin mRNAs. The paraventricular and supraoptic nuclei were examined in all studies and the arcuate nucleus and pituitary gland in the acute withdrawal study. 3. Neither acute nor chronic morphine administration altered either (a) hypothalamic parvocellular or magnocellular CRF mRNA, or (b) anterior pituitary or pars intermedia POMC mRNA. 4. Naloxone-precipitated morphine withdrawal resulted in a marked increase in parvocellular (but not magnocellular) CRF mRNA within 4 h and levels remained elevated through 24 h. There was no change in arcuate nucleus or pars intermedia POMC mRNA, but in the anterior pituitary there was a delayed increase, significant at 24 h. 5. Simple morphine withdrawal without the use of naloxone did not result in any change in CRF mRNA but there were increases in magnocellular vasopressin and dynorphin mRNA, presumably related to decreased water intake. 6. Intraperitoneal hypertonic saline stress also resulted in a marked accumulation of both parvocellular CRF and vasopressin mRNA without any concomitant change in magnocellular vasopressin mRNA. Increased translation of CRF mRNA was also evidenced by increased immunoreactive CRF detected by immunocytochemistry.
Animals↗
Inhibition of vasopressin secretion during migraine.
Six subjects with a history of increased urinary frequency during migraine were studied. In each case there was a marked diuresis and natriuresis within 12 hours of onset of the headache. This was associated with a significant fall in urinary arginine vasopressin (AVP) (p less than 0.01). Migraine may be associated with altered hypothalamic activity resulting in reduced AVP secretion.
Adult↗
Role of atrial pressure and rate in release of atrial natriuretic peptide.
To investigate whether atrial natriuretic peptide (ANP) release during paroxysmal tachycardia is due to increased atrial rate or increased atrial pressure, plasma ANP concentrations were measured during atrial pacing at increasing rates in six alpha-chloralose-anesthetized dogs whose atrial pressures were maintained artificially low by balloon occlusion of the inferior vena cava (IVC). These ANP concentrations were compared with those seen during identical increasing atrial rates in the same dogs without IVC occlusion. During incremental pacing without IVC occlusion, pulmonary wedge pressure (PWP; mean +/- SE) rose progressively from 5.3 +/- 1.6 at 200 to 20.2 +/- 2.3 mmHg at 350 beats/min (P less than 0.01), and right atrial pressure (RAP) rose progressively from 2.5 +/- 0.9 at 200 to 6.7 +/- 2.1 mmHg at 350 beats/min (P less than 0.05). At the same time, arterial and coronary sinus ANP concentrations rose from 116 +/- 55 and 339 +/- 91 to 1,126 +/- 226 and 1,960 +/- 456 pmol/l, respectively (P less than 0.01). In contrast, incremental pacing with IVC occlusion produced no significant increase in PWP and RAP. Arterial and coronary sinus ANP concentrations during IVC occlusion were, respectively, 208 +/- 126 and 388 +/- 159 at 200 and 261 +/- 83 and 345 +/- 80 pmol/l at 350 beats/min (NS). This study demonstrates that the release of ANP during tachycardia is primarily dependent on increased atrial pressure and not atrial rate.
Animals↗
Atrial natriuretic peptide inhibits postural release of renin and vasopressin in humans.
The effects of infusions of atrial natriuretic peptide (ANP) on the hormonal and hemodynamic responses to head-up tilt were investigated in six healthy adults. Head-up tilt at 45 degrees for 2 h during placebo saline infusion caused a 7% fall in blood volume accompanied by increases in plasma renin activity (PRA) and plasma arginine vasopressin (AVP) of 112 and 175%, respectively. Head-up tilt was repeated during an infusion of ANP producing a four- to sixfold increase in plasma ANP concentrations. This resulted in an 18% fall in plasma volume, yet despite this greater fall in plasma volume, PRA did not change. Two subjects experienced vasovagal symptoms toward the end of the ANP infusions accompanied by large increases in plasma AVP. In the other four subjects, plasma AVP remained unchanged during ANP infusions. Both procedures resulted in similar increases in plasma norepinephrine levels and in heart rate. Infusion of ANP prevents the posturally stimulated release of renin and AVP.
Adult↗
The neuroendocrine paraventricular hypothalamus: receptors, signal transduction, mRNA and neurosecretion.
The hypothalamus is one of the most studied areas of the central nervous system. Many of its functions are understood and there is an extensive literature on its role in the control of pituitary hormone secretion, autonomic nervous system activity, regulation of salt, water and food ingestion, body temperature regulation and aspects of behaviour. Although the role of the hypothalamus in the control of pituitary secretion was postulated in the early 1900s, the chemical nature of these control mechanisms has only been documented in the last few years. The opioid peptides represent one particular family of chemical compounds which have been shown to have many effects on pituitary hormone secretion. Exogenous opioids inhibit the neurosecretion of both vasopressin and oxytocin from the posterior pituitary neurosecretory terminals of hypothalamic cell bodies. Opioids also have major actions on the secretory activity of the anterior pituitary which has no innervation from the hypothalamus, but which is regulated by blood-borne factors in the hypophyseal portal circulation which runs from the median eminence of the hypothalamus. It was therefore of considerable interest when it was discovered that endogenous opioid peptides could be detected both in the neurohypophyseal system and in cells which project into the median eminence. The simple presence of a peptide in a neurone does not necessarily imply a function. If, however, we can demonstrate that regulation of the synthesis of the peptide occurs in a manner which corresponds with the expected role of the agent, this provides powerful data in support of a genuine physiological function. The elucidation of the genomic structure of the precursors for the three endogenous opioid peptides has provided us with the ability to measure mRNA for these peptides in defined areas of the brain and to assess their response to appropriate stimuli. Not only does mRNA for the endogenous opioid dynorphin coexist in the same cells as vasopressin but we have now been able to demonstrate that stimuli to vasopressin secretion also result in a markedly increased accumulation of dynorphin mRNA. Similarly, previous studies have shown that opioid peptides derived from another precursor--pro-enkephalin A--coexist with corticotrophin releasing factor in a different group of hypothalamic cells. We have now been able to demonstrate that stresses which result in an accumulation of corticotrophin releasing factor mRNA also result in increased pro-enkephalin mRNA in the same area. This considerably strengthens the hypothesis that endogenous opioids do play a significant role in the control of hypophyseal secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A short water deprivation test incorporating urinary arginine vasopressin estimations for the investigation of posterior pituitary function in children.
The value of a 7-h water deprivation test incorporating urinary osmolality and urinary arginine vasopressin (AVP) measurements was investigated in 20 children with suspected anterior or posterior pituitary dysfunction (group A) and 11 presenting with polyuria and polydipsia (group B). A control group of 16 healthy children was also studied. Urinary osmolalities in the control subjects after 7 h of water deprivation were 827-1136 mosmol/kg and urinary AVP 114-320 pmol/l. Of the group A patients, 5 had symptomatic diabetes insipidus with urinary osmolalities less than 300 mosmol/kg, and urinary AVP concentrations of less than 10 pmol/l, and 5 had normal urinary concentrating ability. The other 10 patients had varying degrees of partial diabetes insipidus (urinary AVP 6-53 pmol/l) although in 3 urinary concentrating ability was well maintained (osmolality 650-747 mosmol/kg). In group B, a diagnosis of compulsive water drinking was made in 9 patients, 1 had nephrogenic diabetes insipidus (urinary osmolality 68 mosmol/kg, AVP 782 pmol/l), and the final patient had transient diabetes insipidus. The test described was easy to perform and well tolerated even in young children. Using this test alone, it was possible to identify patients with partial defects of posterior pituitary function even when urinary concentrating ability was maintained, as well as those with complete cranial diabetes insipidus, nephrogenic diabetes insipidus, and compulsive water drinking.
Adolescent↗
Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.
The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.
Animals↗
Opioid-mediated inhibition of oxytocin during insulin-induced hypoglycemic stimulation of vasopressin in man.
We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulin-induced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P less than 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Saline-infused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 +/- 0.4 pmol/l before insulin to 3.2 +/- 1.3 pmol/l at 45 min (P less than 0.05). We conclude that there is opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.
Adult↗
Quantitative in-situ hybridization histochemistry of anterior pituitary hormone mRNA species in human pituitary adenomas.
We have examined the anterior pituitary hormone messenger (m) RNA species contained in biopsies of 41 pituitary tumours obtained at hypophysectomy using in-situ hybridization histochemistry. The adenoma were grouped clinically into 12 prolactinomas, 8 somatotrope adenomas, 16 non-functioning, 4 Nelson's syndrome, and 1 thyrotrope adenoma. Of these, 10 contained no detectable anterior pituitary hormone mRNA species and 11 appeared to be expressing the gene responsible for the patients' clinical state in isolation. In a number of cases the accumulation of specific mRNA species was not accompanied by an increase in the circulating levels of the corresponding hormone or subunit. Evidence of activation of more than 1 anterior pituitary hormone gene was present in 16 adenomas of which only 7 showed a pattern of activation or amplification of gene expression which would suggest deregulation of either the inositol phospholipid or cAMP second messenger pathway. It was therefore not possible from these data to postulate that isolated deregulation of a single second messenger transduction pathway is a common etiological factor in pituitary tumour formation.
Adenoma↗