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Biomedical subjects

M L Forsling

Publications and source records attributed to M L Forsling.

At least 109 records · Page 6Linked to original sources

Arginine vasopressin dissociates the diuresis and natriuresis due to atrial natriuretic factor in man.

The possible interaction between arginine vasopressin (AVP) and atrial natriuretic factor (ANF) in the control of urinary sodium and water excretion was investigated in man. Nine healthy male volunteers undergoing stable maximal water diuresis were studied on four separate occasions. Atrial natriuretic factor 15 pmol kg-1 min-1 or placebo (P) was concomitantly administered against a background infusion of either AVP 0.003 pmol kg-1 min-1 or P; thus the combinations P + P, AVP + P, P + ANF and AVP + ANF were studied. Atrial natriuretic factor caused a significant increase in sodium excretion (UNaV) [+56%], urinary flow rate (V) [+17%] and free water clearance (CH2O) [+23%]; creatinine clearance (Ccr) did not change. Arginine vasopressin reduced V (-58%) and CH2O (-68%) but did not alter UNaV or Ccr. On the AVP + ANF study day, UNaV increased (+64%) as with P + ANF, but V (-44%) and CH2O (-52%) continued to decrease below baseline levels; analysis of variance showed this antidiuresis reflected the prevalent effect of AVP rather than any specific interaction. These results show that AVP is able to dissociate the natriuretic and diuretic effects of ANF.

Adult↗

Changes in vasopressin and cortisol secretion during operant drinking in dehydrated pigs.

Two studies were carried out to examine endocrine changes during a 60-min period of operant drinking in 24-h dehydrated pigs. Measurements were made of water intake, osmolality, hematocrit, and plasma concentrations of lysine vasopressin (LVP) and cortisol during rehydration (experiment 1) and of fluid intake, osmolality, and LVP levels during consumption of isotonic saline (experiment 2). Increases in osmolality and LVP produced by dehydration in experiment 1 were rapidly reversed during rehydration with the result that osmolality returned to predeprivation levels after 20 min and LVP after 30 min, but there was no evidence of a decrease in LVP before absorption. Plasma cortisol concentrations were unaffected by dehydration although they declined during the final 40 min of experiment 1. In experiment 2, osmolality remained elevated during saline drinking, but plasma concentrations of LVP declined abruptly. The results suggest that oropharyngeal factors inhibiting vasopressin release, revealed during saline ingestion, are obscured during normal rehydration as a result of the rapid rate at which water is absorbed by the gut in this species.

Animals↗

Natriuretic action of arginine vasopressin in the conscious unrestrained rat.

A method for studying the renal action of AVP in the saline-infused conscious unrestrained rat is described. Conscious rats infused iv with 0.077 mol/l NaCl at 150 microliter/min had a plasma AVP concentration of 0.70 +/- 0.15 mol/l. AVP administration at 6 and 24 microU/min resulted in plasma AVP levels of 0.97 +/- 0.14 and 2.27 +/- 0.30 mU/l, respectively. AVP administration at 6 microU/min increased Na+ excretion from 11.9 +/- 0.80 to 14.0 +/- 0.9 mumol/min and at 24 microU/min AVP raised Na+ excretion from 10.3 +/- 0.7 to 14.0 +/- 1.1 mumol/min. The increases were accompanied by the expected reductions in urine flow. As the changes in plasma AVP are within the range occurring in response to moderate dehydration, the observed increases in Na+ excretion provide support for the view that AVP is involved in the physiological regulation of Na+ excretion.

Animals↗

A comparison of the vasopressin response of rats to intraperitoneal and intravenous administration of hypertonic saline, and the effect of opioid and aminergic antagonists.

The vasopressin response of rats to i.p. injection of hypertonic sodium chloride (1.5 mol/l) was compared with that following i.v. infusion of 1.05 mol sodium chloride/l. The two regimes produced a similar vasopressin response in terms of the osmotic threshold, although the slopes of the plot of plasma vasopressin levels against plasma osmolality were not identical. Pretreatment with naloxone and levallorphan increased the resting vasopressin levels and effectively potentiated vasopressin release in response to hypertonic saline by reducing the osmotic threshold for hormone release. Thus, opioid peptides appear to exert an inhibitory effect on vasopressin release under resting and stimulated conditions. The adrenoreceptor antagonists propranolol, phenyoxybenzamine and phentolamine produced a fall in resting vasopressin concentrations while propranolol and phenoxybenzamine potentiated the osmotic release of vasopressin in association with a fall in the osmotic threshold. This would suggest that noradrenergic pathways are excitatory at rest while having an inhibitory effect on the osmotic response. Metoclopramide also produced a fall in resting plasma vasopressin concentrations while increasing the osmotic response. In contrast haloperidol did not affect the vasopressin response.

Animals↗

Pituitary and plasma vasopressin concentrations and fluid balance throughout the oestrous cycle of the rat.

Observations were made of fluid balance and vasopressin concentrations throughout the oestrous cycle of normally cyclic female rats housed under a 12 h light: 12 h darkness regime. Plasma vasopressin concentrations were found to increase progressively during the light period, falling again during the night on all days of the cycle except pro-oestrus. On this day, peak vasopressin concentrations of 3.32 +/- 0.8 pmol/l were seen between 10.00 and 12.00 h, with lower concentrations of 1.74 +/- 0.22 pmol/l being seen between 18.00 and 19.00 h. Urine flow appeared to reflect the changes in plasma vasopressin concentrations, being significantly lower during the light phase, with a small increase being seen over this period on pro-oestrus. Pituitary vasopressin concentrations were highest between 09.00 and 10.00 h and fell progressively over each of the 4 days of the oestrous cycle. The changes in pituitary content were greater than could be accounted for in terms of the alterations in the plasma concentrations of vasopressin.

Animals↗

Separate mechanisms for central osmotically-induced drinking and vasopressin release in minipigs.

Operant drinking and lysine vasopressin (LVP) release were investigated in minipigs following intracerebroventricular (ICV) injections of hypertonic equiosmolar (1.4 osM) solutions of NaCl and of sucrose and mannitol dissolved in 0.15 M NaCl or water, and of urea dissolved in 0.15 M NaCl. Hypertonic (0.74 M) NaCl produced significant drinking and LVP release in all minipigs tested whereas hypertonic equiosmolar (1.4 osM) solutions of sucrose and mannitol induced only drinking. Mannitol, both with and without NaCl, was more effective than sucrose. Hypertonic urea was ineffective both as an osmotic dipsogen and at stimulating the release of LVP. These results suggest that two independent mechanisms could be involved in drinking and LVP responses to ICV administration of hypertonic solutions in minipigs.

Animals↗

Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man.

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means +/- SD) of 3.9 +/- 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 +/- 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 +/- 4.6 pg/ml on the fifth day of the high sodium diet. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.

Adult↗

Altered water excretion in healthy elderly men.

The renal and vasopressin (AVP) response to a standard oral water load (20 ml/kg) was examined in a group of water-replete healthy elderly men (n = 6). Two groups, respectively, of water-replete and water-deprived young healthy volunteers acted as controls. After 2 h, the old group had excreted 41 +/- 2.4% (mean +/- SEM) of the water load compared to 100.7 +/- 8.8% in the water-replete young group and 70 +/- 3.8% in the water-deprived young group (P less than 0.01). Similarly, peak diuresis (7.01 +/- 0.48 ml/kg) and peak free-water clearance (5.7 +/- 0.48 ml/min) as determined from hourly sampling in the old group were delayed and significantly less than both young groups (P less than 0.01) (peak diuresis, young water-replete, 10.86 +/- 0.56 ml/kg, young water-deprived, 10.2 +/- 0.64 ml/kg, peak free-water clearance, young water-replete 8.4 +/- 0.72 ml/min, young water-deprived 9.5 +/- 0.88 ml/min). When these indices were adjusted for reduced creatinine clearance (Ccr) in the elderly, there was no significant difference between the young and old groups. Plasma AVP decreased similarly in all three groups following ingestion of water but there was no significant difference in mean plasma AVP between the young and old subjects throughout the study period. We therefore conclude that ability to excrete excess water promptly is impaired in healthy elderly men. This defect is due, at least in part, to an age-related reduction in glomerular filtration rate.

Adult↗

Endocrine and behavioural factors affecting water balance in sheep subjected to isolation stress.

The effect of stress on drinking, water balance and endocrine profile was studied using ten castrated rams. Individual sheep were exposed to 30-h periods of total isolation (psychological stress) or physical separation from their social group (control). Plasma was analysed for haematocrit, osmolality, electrolyte levels and concentrations of cortisol and arginine vasopressin. Isolation stress significantly reduced water intake, increased haematocrit and plasma concentration of cortisol, but did not alter osmolality or vasopressin concentration. The physiological effects of this self-imposed water restriction contrast with those obtained by depriving the sheep of water for 24 h under conditions that were not stressful, i.e. by keeping them grouped together. These results suggest that cortisol may act to defend plasma volume in sheep exposed to acute stress. The results also indicate that vasopressin probably should not be considered to be a 'stress hormone' in the sheep.

Animals↗

Plasma concentrations of vasopressin and a prostaglandin F2 alpha metabolite in women with primary dysmenorrhoea before and during treatment with a combined oral contraceptive.

Oral contraceptives reduce menstrual pain but the interaction with vasopressin and prostaglandin F2 alpha, two uterine stimulants related to the condition, is unknown. Ten women with a history of moderate to severe dysmenorrhoea were studied. Repeated blood samples were taken during a first menstrual cycle without treatment, during the first 21 days of a second cycle when they received an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethynyloestradiol) and on the first or second day of the bleeding following hormonal withdrawal. Measurements were made of plasma concentrations of arginine vasopressin, 15-keto-13,14-dihydroprostaglandin F2 alpha, oestradiol-17 beta, progesterone, ethynyloestradiol, levonorgestrel, FSH, LH and prolactin, and serum osmolality was measured. Seven of the women rated their discomfort as moderate to severe on the first two menstruations, but as none or light at the withdrawal bleeding; with the rating scale for degree of pain that was used, this decrease in pain was significant (P less than 0.001). The plasma concentration of vasopressin in these seven women showed significant variation, with the highest concentrations being obtained at the beginning of the two painful menstruations (3.76 +/- 0.76 and 1.75 +/- 0.30 (S.E.M.) pmol/l) and at ovulation in the control cycle (1.91 +/- 0.58 pmol/l). During treatment the concentrations were consistently low, except on the first day of withdrawal bleeding (2.33 +/- 0.35 pmol/l). The concentrations of the prostaglandin F2 alpha metabolite showed less variation, but again the values at withdrawal bleeding (271 +/- 39 pmol/l) were not different from those obtained over the painful menstruations (255 +/- 24 and 217 +/- 25 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of aging on vasopressin secretion, water excretion, and thirst in man.

Disorders of water balance are common among elderly patients. A number of factors may contribute. Osmoreceptor-mediated release of AVP is increased, but the response to volume stimuli may be reduced. The capacity of the kidney to concentrate urine is reduced by age, but this impairment cannot be correlated with coincident loss of glomerular filtration (GFR); there may rather be a failure of cAMP response to AVP in aging kidneys. Free water clearance is reduced in the old in proportion to the loss of GFR. Thirst mechanisms are also significantly impaired in healthy as well as sick old people. This combination of factors renders old people particularly liable to develop disorders of water homeostasis during episodes of acute or chronic ill health.

Aging↗

Selective renal medullary damage and hypertension in the rat: the role of vasopressin.

The induction of selective renal medullary damage by 2-bromoethylamine hydrobromide (BEA) results in polyuria and raised blood pressure. In view of the likely elevation of plasma vasopressin we have investigated the role of vasopressin (AVP) in the elevated blood pressure in this model. Plasma vasopressin levels in BEA pretreated rats were raised significantly (2 +/- 0.6 pg/ml vs 0.8 +/- 0.1 in normal rat, P less than 0.05) but not to pressor levels. In addition, pressor responsiveness was investigated in renal medullary damaged rats. There was a reduced response to vasopressin and noradrenaline but no alteration with angiotensin II. A specific V1, receptor AVP antagonist [d(CH2)5Tyr(Me)AVP] produced no fall in blood pressure but returned the noradrenaline dose-response curve to normal. This suggests an interaction between vasopressin and the sympathetic nervous system in this model. Thus there is no evidence that vasopressin contributes to the rise in blood pressure produced by chemical renal medullectomy and other mechanisms have to be sought.

Angiotensin II↗

Effect of haemorrhage on plasma lysine vasopressin and the cardiovascular responses to vasopressin in the pig fetus.

The effect of haemorrhage on plasma lysine vasopressin concentrations and the cardiovascular effects of intravenous injections of synthetic lysine vasopressin were studied in twenty-four chronically catheterized pig fetuses aged between 81 and 114 d gestation (term = 114 +/- 1 d). Removal of 15-20% of the estimated blood volume reduced mean arterial blood pressure and elevated plasma vasopressin concentrations above the mean basal value of 2.2 +/- 0.3 muu./ml. The vasopressin concentration in plasma of fetuses younger than 104 d was insignificantly affected at 30 and 60 min after the bleed, whereas the corresponding values in older fetuses were raised by 12.7 +/- 7.2 muu./ml (d.f. = 7) and 16.0 +/- 6.0 muu./ml (d.f. = 7) respectively. The pituitary concentration of vasopressin was also greater towards the end of gestation. Plasma osmolality was unaffected by fetal blood loss. Maternal concentrations of vasopressin did not change from the basal values of 1.0 +/- 0.1 muu./ml (d.f. = 16). Injection of vasopressin raised fetal blood pressure and decreased heart rate. These results demonstrate that lysine vasopressin is present in the circulation of the pig fetus at 81 d (0.72 gestation), and that near term fetuses respond to haemorrhage more rapidly, and to a greater degree than younger fetuses.

Animals↗

The influence of neurohypophysial hormones on renal function in the acutely hypophysectomized rat.

1. Renal function and the effect of neurohypophysial hormone replacement was investigated in anaesthetized, acutely hypophysectomized, male rats. 2. Although urine production was only slightly lower over the 8 h post-operative study period in hypophysectomized rats, sodium excretion was greatly depressed reaching only 3.5 +/- 1.4 mumol/min compared with a peak of 13.2 +/- 1.0 mumol/min in intact animals. 3. In association with a decline in mean arterial blood pressure, glomerular filtration rate in hypophysectomized rats fell to 2.1 +/- 0.2 ml/min 8 h after operation by comparison with a mean rate in intact rats of 3.2 +/- 0.2 ml/min. 4. Plasma corticosterone levels were much lower in hypophysectomized (4 +/- 2 ng/ml) than in intact (36 +/- 4 ng/ml) rats, plasma aldosterone was reduced to a lesser extent (0.41 +/- 0.08 compared with 0.76 +/- 0.04 ng/ml). While oxytocin was not detectable in hypophysectomized rat plasma, trace levels of vasopressin (0.16 +/- 0.04 mu u./ml) were found. In intact unanaesthetized rats basal plasma levels of oxytocin were 0.32 +/- 0.13 mu u./ml and vasopressin were 0.85 +/- 0.19 mu u./ml. 5. Administration of oxytocin at 150 mu u./min, which produced plasma hormone levels (24.0 +/- 2.5 mu u./ml) greatly in excess of basal concentrations, increased renal sodium excretion but did not alter urine flow. Oxytocin administration at the lower rate of 15 mu u./min producing plasma hormone levels of 2.60 +/- 0.1 mu u./ml, did not alter renal sodium excretion. 6. Arginine vasopressin administered at 12 mu u./min induced plasma hormone levels of 1.54 +/- 0.09 mu u./ml and produced a large antidiuresis and small increase in the rate of sodium excretion. 7. The natriuretic response to vasopressin was potentiated by concurrent administration of oxytocin at 15 mu u./min. The peak sodium excretion of 5.8 +/- 1.0 mumol/min, however, remained well below that seen in intact rats. 8. It is concluded that, as restoration of posterior pituitary hormones at or above the physiological range only partially restored sodium excretion, the absence of anterior pituitary factors may also contribute directly or indirectly to the renal sodium retention of the hypophysectomized rat.

Animals↗

A synergistic effect of oxytocin and vasopressin on sodium excretion in the neurohypophysectomized rat.

1. Renal function and the effect of oxytocin and vasopressin replacement have been examined in anaesthetized male neurohypophysectomized rats. 2. Rates of urine flow were higher but sodium excretion markedly lower in neurohypophysectomized rats than in intact animals receiving hypotonic saline infusion (33.8 +/- 2.3 vs. 27.0 +/- 0.7 ml and 472 +/- 84 vs. 1946 +/- 124 mumol respectively for the third to sixth hour of study). 3. In intact animals, mean arterial blood pressure stabilized at 106 mmHg. Haematocrit (46%) remained stable but glomerular filtration rates declined slightly over the 8 h of study to 2.5 +/- 0.2 ml/h. These values in neurohypophysectomized rats did not differ significantly from those in intact rats. 4. Although plasma corticosterone levels (54 +/- 13 ng/ml) did not differ significantly from those in intact rats, neurohypophysectomy was associated with greatly reduced aldosterone concentration (0.12 +/- 0.03 vs. 0.76 +/- 0.04 ng/ml). Trace levels of vasopressin (0.17 +/- 0.03 microunit/ml) were found in neurohypophysectomized rat plasma. 5. Oxytocin administration at 15 microunits/min, which produced plasma hormone levels of 1.62 +/- 0.19 microunit/ml, had no detectable effect on sodium excretion but increased urine flow. Arginine vasopressin administration (12 microunits/min) inducing plasma levels of 1.24 +/- 0.08 microunit/ml, reduced urine flow by 80% and produced a small increase in sodium excretion. 6. Concurrent administration of oxytocin (15 microunits/min) potentiated the natriuretic response to vasopressin (12 microunits/min). Total sodium excretion during the 3 h combined hormone infusion (1256 +/- 149 mumol) greatly exceeded that in animals receiving vasopressin alone (549 +/- 132 mumol) and approached that observed in intact animals (1946 +/- 124 mumol). Combined hormone administration at the lower rate of 5 microunits/min oxytocin and 4 microunits/min vasopressin produced a similar large increment in sodium excretion. 7. It is concluded that replacement of both neurohypophysial hormones, at plasma levels within the physiological range, largely reverses the renal sodium retention of neurohypophysectomized rats, oxytocin considerably potentiating the natriuretic action of vasopressin. This synergism between the two neurohypophysial peptides to promote salt excretion may be an important component of the non-steroidal management of sodium.

Animals↗

Stimulus for vasopressin release during elective intra-abdominal operations.

In 12 patients undergoing an upper abdominal operation, blood pressure and peripheral venous blood samples were taken at intervals throughout the procedure. There was no significant increase in plasma vasopressin concentration after induction of anaesthesia or skin incision; within 3 min of opening the peritoneum and commencing intraperitoneal manipulation there was a highly significant rise (P less than 0.01), maintained with fluctuations until closure of the abdomen. There was no correlation between the changes of blood pressure and those in plasma vasopressin level. In 16 patients undergoing elective cholecystectomy similar observations were made to coincide with events believed, on the basis of the first study, to be related to changes in the concentration of vasopressin. There was a significant rise in vasopressin concentration (P less than 0.01) after incision of the peritoneum, 1 min after the start of intraperitoneal manipulation (P less than 0.01) and after deliberate traction on the stomach (P less than 0.01). During operative cholangiography, when there was no intraperitoneal manipulation, there was a significant fall in the vasopressin level. There was no correlation between changes in vasopressin concentration and blood pressure. These findings indicate that during an abdominal operation nervous stimuli, arising from within the peritoneal cavity and probably mediated via the autonomic system, are an important factor responsible for the increased secretion of vasopressin, and, at least in the absence of major changes in blood pressure and osmolality, the determinant factor.

Abdomen↗

Angiotensin II-induced thirst and vasopressin release in man.

1. The thirst and plasma vasopressin responses to single-blind controlled intravenous angiotensin II infusions (2-16 ng min-1 kg-1) were investigated in ten healthy young men. 2. Thirst and vasopressin secretion were stimulated in four out of ten subjects. These effects occurred at plasma angiotensin concentrations well above those measured under physiological conditions associated with thirst and vasopressin secretion such as water deprivation. 3. Further studies are needed to define why only certain individuals respond to intravenous angiotensin II infusions and to determine whether potentiation of angiotensin-induced thirst and vasopressin secretion by other stimuli (e.g. hypovolaemia and hypertonicity) might occur in man, in particular under pathological conditions when plasma angiotensin levels are above the physiological range.

Adult↗