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Biomedical subjects

M L Forsling

Publications and source records attributed to M L Forsling.

At least 127 records · Page 7Linked to original sources

The effect of vasopressin on solute and water excretion during and after surgical operations.

The relationship between the concentration of plasma arginine vasopressin (AVP), urine volume, and osmolality during and after an abdominal operation was studied in nine patients. In all patients the AVP level rose well above that necessary for maximal antidiuresis (5 fmol ml-1) and then returned to within the normal range (0.5-5.0 fmol ml-1) usually over the next 24 hours. During this period of raised AVP concentration the urine volume, which varied considerably, was closely related to osmolar excretion. With the fall of AVP to normal levels, all but one of the patients eventually exhibited positive free water clearance. However, in most patients the urine remained hypertonic for some hours and its volume continued to be determined mainly by osmolar load which was itself apparently related to glomerular filtration rate. At no time was there a significant relationship between changes in plasma AVP concentration and urinary volume.

Aged↗

Somatostatin and water excretion in man: an intrarenal action.

Intravenous infusion of somatostatin in six water loaded normal human subjects produced a prompt reduction in urine flow accompanied by a rise in urine osmolality and a decrease in free water clearance. Plasma AVP levels did not change. Somatostatin would seem to exert an antidiuretic effect directly on the kidney.

Adult↗

Osmotic thirst and vasopressin release in humans: a double-blind crossover study.

Thirst is a subjective sensation. Therefore to investigate further the nature, intensity, and specificity of osmotic thirst, we studied the effects of double-blind infusions of hypertonic (0.45 M) and isotonic (0.15 M) saline on subjective ratings and sensations of thirst, water intake, plasma vasopressin, and body fluids in seven healthy volunteer young men. Only the hypertonic saline significantly increased plasma sodium concentration, plasma osmolality, plasma vasopressin concentration, and visual analog ratings of thirst sensations. Both infusions expanded blood volume, which was greater with the hypertonic saline infusion. Neither solution significantly altered mean arterial blood pressure nor plasma angiotensin levels. Throughout a 60-min drinking period after the infusions, water intake was always significantly greater after the hypertonic saline than after the isotonic saline. The subjects described the thirst sensations as mainly due to a dry unpleasant tasting mouth, which was promptly relieved by drinking. Visual analog rating changes confirmed the subjective reports. Finally, the effects on thirst and vasopressin secretion were observed at plasma sodium concentration and osmolality changes that are well within the physiological range.

Adult↗

The vasopressin response to microinjections of norepinephrine into the brain of the conscious pig.

The possibility that the amygdala influences the release of vasopressin has been raised by the observation that electrical stimulation of this area results in vasopressin release in the conscious animal. Therefore the effect on vasopressin concentrations has been studied by microinjections of norepinephrine into the amygdala of the conscious miniature pig. The studies were performed on castrated male and female pigs with chronically implanted cannulae in the brain and in the external jugular vein. Lysine vasopressin concentrations were determined using a specific sensitive radioimmunoassay. Microinjections of 1 microliter 0.12 M sodium chloride were without effect. Injections of norepinephrine in the dose range 10(-4)-10(-10) M had no effect in the male animal but a significant vasopressin response could be obtained in the females.

Amygdala↗

The stimulus for vasopressin release during laparoscopy.

The results of our study have demonstrated raised AVP secretion during laparoscopy, which was stimulated by the maximal increase in IAP. We propose that this relationship is mediated by way of known hemodynamic pathways occurring during laparoscopy involving a reduction in intrathoracic blood volume.

Abdomen↗

Reduced thirst after water deprivation in healthy elderly men.

To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin.

Adult↗

Perinatal development of tubular function in the pig.

Renal tubular function has been studied in pig fetuses of 105-112 d gestational age in new-born pigs 5-9 d old. The experiments were performed on anaesthetized animals, urines being collected by inserting a catheter into one ureter of the animal under study. The glomerular filtration rate was estimated and plasma concentrations and urinary excretion of the following substances were measured: sodium, potassium, calcium, ammonia, urea, phosphate, glucose fructose, creatinine, protein and exogenous 4-aminohippuric acid, and inulin. The reabsorption of water was considered in relation to the plasma vasopressin values. New-born pigs were loaded with glucose and fructose in order to determine the maximal tubular transport rate of these substances. Significant changes at birth occur in only a few functions of the tubulus system. Following delivery, major changes are: (1) the increased reabsorption of sodium and water which is probably the most important adaptation to extra-uterine life; (2) an apparent increasing impermeability of the tubular epithelium for creatinine, and (3) the direction of transport of fructose, which is reabsorbed by fetuses whereas neonates demonstrate a net secretion. Glucose and fructose are transported by different mechanisms. The experiments with fructose-loaded piglets demonstrate that there are at least two transport mechanisms for fructose: reabsorption - either passive or active - and secretion. The factors causing a shifting from one mechanism to the other are not yet known.

Absorption↗

Central effects of dopamine on vasopressin release in the normally hydrated and water-loaded rat.

The effect of intracerebroventricular (I.C.V.) micro-injections of dopamine on vasopressin (AVP) release was investigated in normally hydrated and hydrated rats anaesthetized with urethane, hormone concentrations being determined by radioimmunoassay. Dopamine given in doses of less than 25 micrograms had little effect on AVP concentrations already elevated as a result of anaesthesia and surgery. Doses of over 25 micrograms produced a transient increase in AVP concentrations followed by a fall. Both the increase and the fall were statistically significant. Pimozide (400 micrograms/kg) blocked the fall in AVP concentrations following dopamine. A fall was still seen after the administration of haloperidol (400 micrograms/kg) but it was only significant 20 min after the injection of dopamine. The changes in AVP concentration after the administration of naloxone (400 micrograms/kg) were not statistically significant. In water-loaded rats I.C.V. micro-injections of dopamine produced a dose-dependent antidiuresis over the range 1-25 micrograms. An injection of 25 micrograms dopamine in these animals produced an increase in AVP concentrations to 1.8 +/- 0.51 microunits/ml and a fall in urine flow which could be approximately matched by an infusion of vasopressin of 15 microunits/min. The antidiuresis in response to dopamine could be blocked by haloperidol. The response to dopamine in the anaesthetized animals depends on a number of factors including the initial activity of the neurohypophysial system.

Animals↗

Natriuretic response of the rat to plasma concentrations of arginine vasopressin within the physiological range.

The relationship of plasma vasopressin concentrations in the physiological range to renal electrolyte excretion was investigated. Unanaesthetized rats, when normally hydrated, were found to have a plasma vasopressin concentration of 1.13 +/- 0.15 mu u./ml. 16 h water deprivation raised this to 1.98 +/- 0.21 mu u./ml. Inactin-anaesthetized rats infused with 0.45% NaCl had a plasma vasopressin concentration of 1.19 +/- 0.18 mu u./ml. Administration of synthetic arginine vasopressin at 6 and 24 mu u./min raised plasma vasopressin levels to 1.88 +/- 0.17 and 4.26 +/- 0.43 microunits./ml respectively. In addition to the expected antidiuresis, vasopressin at a rate of 6 microunits./min also produced a highly significant increase in Na+ excretion from 8.9 +/- 0.6 to 10.5 +/- 0.6 mumol/min and Cl- excretion from 9.1 +/- 0.7 to 10.5 +/- 0.7 mumol/min. At 24 microunits./min it produced larger increases in Na+ and Cl- excretion. Inactin-anaesthetized hypophysectomized rats infused with 0.45% NaCl had a plasma vasopressin concentration of only 0.17 +/- 0.04 microunits./ml. Administration of vasopressin at 6 and 24 microunits./ml raised plasma vasopressin levels in these animals to 0.63 +/- 0.17 and 2.20 +/- 0.11 microunits./ml respectively. Hypophysectomized rats failed to exhibit a natriuresis in response to the lower dose of vasopressin, despite exhibiting an undiminished antidiuresis. The failure of the natriuresis may be related to the lower plasma vasopressin concentration achieved. It is concluded that in the rat plasma vasopressin concentrations within the physiological range do influence Na+ and Cl- excretion by the kidney as well as controlling urine flow rate.

Animals↗

Hyponatraemia in the first week of life in preterm infants. Part I. Arginine vasopressin secretion.

Continuous sequential urinary arginine vasopressin measurements in 14 preterm, ventilated infants suggest that both osmoreceptor and volume receptor systems are able to stimulate the prolonged secretion of arginine vasopressin from 26 weeks' gestation. The kidney is able to respond to arginine vasopressin stimulation from the first day of life and from 26 weeks' gestation. A maximum urine osmolality not exceeding 550 mOsm/kg was reached which varied with hydration of the infant. Excretion of arginine vasopressin and urine osmolality increased during deterioration of respiratory illness, mask ventilation, bilateral pneumothoraces, and severe intraventricular haemorrhage. The data show that inappropriate arginine vasopressin secretion is common during illness in the first week of life in preterm infants and that strict attention must be paid to water balance during this time.

Arginine Vasopressin↗

Hyponatraemia in the first week of life in preterm infants. Part II. Sodium and water balance.

Serial measurements of plasma sodium, sodium balance, water intake, and urine volume were made for a mean period of 5.9 days in 10 preterm infants of mean gestation 30.5 weeks and mean birthweight 1506 g. In five infants weighed regularly, estimates of insensible water loss averaged 2.6 (range 1.4 to 6.2) ml/kg/hour. High insensible water losses were the cause of hypernatraemia that occurred in two of the 10 infants. Net sodium balance was negative during the study and represented contraction of the extracellular fluid volume associated with weight loss. The negative sodium balance did not seem diminished by increasing sodium intake and there was no evidence that sodium intake need exceed 3 to 4 mmol/kg/day. Hyponatraemia was not due to changes in sodium balance but to water retention associated with inappropriate increases in urinary arginine vasopressin excretion and urine osmolality in 8 of 10 infants. Frequent, accurate measurements of body weight and of plasma sodium are the two most reliable indicators of changes in water balance.

Age Factors↗

Localization and actions of cholecystokinin in the rat pituitary neurointermediate lobe.

Rat pituitary neural lobe contained high concentrations of cholecystokinin-like immunoreactivity (CCK-LI). Section of the pituitary stalk resulted in loss of CCK-LI, and both lactation and replacement of drinking water with 2% saline resulted in marked depletion of CCK-LI. Rats with congenital diabetes insipidus (Brattleboro strain) had a 73% reduction in CCK-LI below the levels of hooded Long-Evans controls, where as levels in the brain were unchanged. Release of CCK-LI, labeled dopamine, and gamma-amino butyric acid in response to potassium depolarization was studied. There was a low fractional release of CCK-LI. Addition of sulfated CCK-8 (CCK-8s) to the medium enhanced the calcium-dependent potassium-stimulated release of dopamine, but basal release was unaffected. gamma-Amino butyric acid release was only poorly calcium dependent and not effected by extracellular CCK-8s. Vasopressin and oxytocin release were stimulated by electrical stimulation of the pituitary stalk, and were unaffected by the addition of CCK-8s to the medium. In vivo, however, the injection of 5 micrograms CCK-8s into the third ventricle resulted in increased plasma vasopressin concentrations.

Animals↗

Vasopressin and prostaglandins in premenstrual pain and primary dysmenorrhea.

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

Adolescent↗

Inhibition of vasopressin effects on the uterus by a synthetic analogue.

A synthetic analogue, deamino-ethyl-oxytocin, which competitively inhibits vasopressin action on uterine activity both in vitro and in animal experiments was developed. The uterine effect of this analogue was studied during the recording of intrauterine pressure in 16 gynecologically healthy women. Increased uterine activity and dysmenorrhea-like pain was induced by infusing lysine vasopressin in a dose of 0.08 microgram/min. Deamino-ethyl-oxytocin inhibited vasopressin action, the threshold dose being approximately 200 micrograms given as a single intravenous injection for about 20 minutes. When given intranasally the drug was also shown to be effective in inhibiting vasopressin-induced uterine activity and symptoms. These results suggest that deamino-ethyl-oxytocin could be of therapeutic value in primary dysmenorrhea, a condition associated with increased vasopressin secretion.

Adult↗

Involvement of prostaglandins in vasopressin stimulation of the human uterus.

The involvement of prostaglandins (PG) in the vasopressin (VP) action on the human uterus was investigated in healthy women during three menstruations. Intrauterine pressure was recorded and total pressure area measured. Repeated plasma samples were taken for estimations of arginine(A)- and lysine(L)-VP, 15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites. During the first menstruation LVP was infused in a dose of 0.08 micrograms/min. During the second menstruation the infusion of LVP was repeated with the same dose, but 70 min before infusion the women received an oral dose of 500 mg of naproxen. During the third menstruation PGF2 alpha was administered intravenously in a dose of 25 micrograms/min. LVP infusion per se caused a significant increase in uterine activity and plasma levels of LVP and PG metabolites. When the women were pretreated with naproxen practically the same uterine activity was induced and closely similar plasma levels of LVP were obtained, but the levels of PG metabolites decreased significantly in comparison with the first series of experiments. Infusion of PGF2 alpha caused an increase in uterine activity but no change in the plasma levels of AVP. The results indicate that uterine stimulation with VP is possible without an obligatory last step of PG synthesis and release. The results also support the concept that an elevated VP level in primary dysmenorrhoea may be of aetiological importance and is not just released as a 'stress'-hormone because of the dysmenorrhoeic pain.

Adult↗

Cerebrospinal fluid arginine vasopressin in degenerative disorders and other neurological diseases.

Arginine vasopressin (AVP) was determined in plasma and lumbar CSF from 46 patients with Parkinson's disease, dementia, cerebrovascular disease, multiple sclerosis and other, mostly peripheral neurological disorders. The mean plasma concentration of AVP was 1.62 microU/ml, the CSF concentration 1.14 microU/ml and the gradient CSF/plasma 0.72. There was a good correlation between the plasma and the CSF values in most patients. No sex difference could be found. A slight decrease of the CSF values could be found with increasing age. Significantly higher CSF-AVP values were found in patients with cerebrovascular disease, whereas lower CSF values were found in patients with dementia and Parkinson's disease. However there were decreased CSF/plasma gradients in patients with dementia and Parkinson's disease to about 0.30 compared to 0.98 in patients with peripheral neurological disorders. Patients with multiple sclerosis had an increased IgG index indicating an intrathecal IgG production but there was no obvious correlation between this and the AVP concentrations in plasma and CSF, nor with the total CSF protein content, nor with the albumin and IgG concentrations in plasma and CSF.

Adolescent↗

Continuous urine collection in the study of vasopressin in the newborn.

We have evaluated the use of urinary vasopressin (AVP) measurements in human newborns to see if urinary AVP excretion is a true reflection of the plasma level. AVP was measured in 37 simultaneously collected plasma and urine samples. The correlation coefficient was 0.8 (p less than 0.001). AVP extracted in duplicate from six urine samples was measured by bioassay and radioimmunoassay. The correlation coefficient was 0.85 (p less than 0.05). To facilitate long-term urine collection we have developed a urine collecting tray to fit a standard incubator or cot. Urinary AVP as measured in 24-hour urine collections in 37 normal infants. AVP excretion was higher in the first 48 h of life than subsequently. Continuous 4-hour urine collections were made in 1 sick infant to assess AVP excretion when urine flow is variable.

Animals↗

Release of vasopressin in response to hypoxia and the effect of aminergic and opioid antagonists.

Plasma vasopressin, arterial blood gas tensions, pH, arterial blood pressure, heart rate and respiration were monitored in conscious rats breathing room air or exposed to varying degrees of hypoxia. A similar series of observations was made in a group of anaesthetized rats and in rats treated with alpha- and beta-adrenergic and dopaminergic blocking agents. The effect of two opioid antagonists on the vasopressin response was also noted. Hypoxia produced an increase in circulating vasopressin concentrations in both conscious and anaesthetized rats. In the conscious animals the increase reached statistical significance when the animals were exposed to 12% oxygen in nitrogen, which produced a fall in arterial PaO2 of 44.7 +/- 5.0%. Guanethidine, phentolamine and propranolol all produced a significant fall in the basal concentrations of vasopressin, while guanethidine, phenoxybenzamine and propranolol blocked the increase seen on breathing 12% oxygen in nitrogen. Naloxone and levallorphan also reduced the vasopressin response to hypoxia. Thus it appears that aminergic pathways play a role in the maintenance of circulating concentrations of vasopressin and in the response to hypoxia. Endogenous opioids also appear to be involved in the hypoxic response.

Animals↗