Oxytocin release and renal actions in normal and Brattleboro rats.
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Animals↗
Biomedical subjects
M L Forsling
Publications and source records attributed to M L Forsling.
Renal response to hypotonic saline load in fetal and new-born pigs.
Kidney function has been studied in pig fetuses (105-109 d of gestation) and neonates (5-7 d old). Urine was collected by catheterization of the ureter. Inulin clearance, the excretion of electrolytes and the osmolality of urine and plasma were measured. In addition the response of the fetal neurohypophysis and fetal and neonatal kidney to a reduction of plasma osmolality was studied. The results show that the inulin clearance increases rapidly in the perinatal period, at a rate greater than would be expected from the gain in body weight. The re-absorption of Na and K is well developed. The fractional sodium excretion in fetuses is 2% and is 0.1% in the new-borns. The urine osmolality is high, probably due to high plasma lysine vasopressin levels persisting throughout the experiment. The infusion of hypotonic saline results in a significant decrease of plasma osmolality but only three out of nineteen animals showed an increase in urine flow. Although lysine vasopressin concentrations fell in some animals the urine stayed hyperosmotic as compared with plasma. The results show that fetuses and neonates may react to volume load but in the conditions of these experiments that regulation of plasma osmolality was inadequate.
Animals↗
The milk ejection reflex in the pig.
1. The milk ejection reflex in response to suckling was studied in conscious sows by continuous recording of intramammary pressure, radioimmunoassay of plasma concentrations of neurohypophysial hormones, and observation of the behaviour of the sows and piglets.2. A regular pattern of nursing, suckling and milk ejection was observed. The mean duration of the suckling period was 6.3 min. Over 144 suckling periods, 113 milk ejections were recorded. Each milk ejection was characterized by a sudden rise in intramammary pressure reaching 20-49 mmHg, and lasting 8-41 sec. Milk ejections occurred only once per suckling period, at a mean interval of 44.3 min.3. Each milk ejection occurred with a mean latency of 2.4 min from the onset of a period of initial massage of the udders by the piglets, and was coincident with a period of quiet suckling when the piglets were consuming milk. The onset of nursing was signalled by the sows grunting in a rhythmic manner. In most cases, the frequency of grunts, at first low, increased suddenly 23 sec before milk ejection.4. During eighteen suckling periods leading to milk ejection, neurohypophysial hormone assays performed on serial blood samples showed an increase in plasma concentration of oxytocin up to 30 sec before milk ejection. The concentration of lysine-vasopressin did not rise above basal levels.5. In 21.4% of the suckling periods, no rise in intramammary pressure was observed. In these ;incomplete sucklings', the sow usually failed to grunt rapidly, and the piglets obtained no milk. For three of these periods, hormone assay showed no increase in oxytocin or vasopressin concentrations in blood.6. Oxytocin given intravenously produced variations in intramammary pressure which depended on the dose and the rate of injection. Rapid injections of 25-50 m-u. oxytocin, caused milk ejections similar to those induced by suckling. When oxytocin was administered at different rates, the faster the injection, the shorter the latency and the higher the amplitude of the response. Plasma concentrations of oxytocin after injection of 25 m-u. were similar to those observed during reflex milk ejection.7. Trains of electrical pulses were applied to the posterior pituitary of four anaesthetized sows. At frequencies of stimulation above 10 Hz, a rise in intramammary pressure and an increase in plasma oxytocin and vasopressin concentrations were observed. At frequencies of stimulation of 30-50 Hz, the response of the mammary gland and the time course of the variations in oxytocin plasma concentrations were similar to those observed during natural reflex milk ejection.8. It is concluded that reflex milk ejections during suckling in the pig are caused by the intermittent and spurt-like release of about 25 m-u. oxytocin, without concomitant vasopressin release. It is postulated that the release of oxytocin is probably precipitated by a brief and massive activation of oxytocin-secreting neurones in the hypothalamus. Central mechanisms controlling the intermittent release of oxytocin are discussed.
Animals↗
The influence of vasopressin on oxytocin-induced changes in urine flow in the male rat.
Oxytocin administration in rat infused with hypotonic saline is associated with a saliuresis and altered renal water excretion. The role of vasopressin in determining the pattern of oxytocin-induced changes in urine flow was investigated in Long Evans and vasopressin-deficient Brattleboro rats, which exhibit contrasting diuretic and antidiuretic responses to oxytocin. Ethanol anaesthesia and water loading in Long Evans suppressed plasma vasopressin levels and was associated with an antidiuretic response to oxytocin. Vasopressin administration in the Brattleboro rat reversed the oxytocin-induced antidiuresis normally observed in vasopressin deficiency. These results taken with previous observations, have been interpreted as indicative that oxytocin acts as a weak agonist at the renal vasopressin receptor. When plasma vasopressin is suppressed or absent oxytocin acts as a weak antidiuretic agent, but in the presence of higher vasopressin levels a diuretic response to oxytocin is seen which follows displacement of vasopressin, the more potent antidiuretic agent, from the renal receptor.
Animals↗
Effect of ovarian steroids on vasopressin secretion.
In normally menstruating women plasma vasopressin concentrations vary with the stage of the cycle and are highest at the time of ovulation and lowest at the onset of menstruation. To determine whether this is the result of changes in the circulating concentrations of ovarian steroids, vasopressin concentrations were determined in six postmenopausal women given oestrogen and progestogen. An increase in plasma oestradiol concentrations to 299 +/- 97.8 pmol/l augmented vasopressin release. Administration of medroxyprogesterone did not influence vasopressin concentrations but when given in combination with oestrogen a fall was observed. Thus it appears that ovarian steroids can modulate vasopressin release.
Animals↗
Dopamine and [D-ALA2, D-Leu5]enkephalin inhibit the electrically stimulated neurohypophyseal release of vasopressin in vitro: evidence for calcium-dependent opiate action.
The effects of both dopamine and enkephalin agonists were assessed on electrically stimulated vasopressin secretion from the isolated neural lobe. Both dopamine (10(-6) M) and the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene; 10(-6) M) significantly reduced the stimulated release of vasopressin. This reduction in vasopressin secretion was prevented by the dopamine antagonist sulpiride (10(-6) M). [D-Ala2, D-Leu5]Enkephalin (DADLE) also inhibited vasopressin release and its effect was additive to that of ADTN. The effect of DADLE was prevented by the opiate antagonist naloxone and was also sensitive to the calcium content of the medium. Low calcium concentrations markedly increased the inhibitory effect of DADLE, while high concentrations abolished its effect. These findings provide evidence of a direct inhibitory action of both dopamine and enkephalins at the level of the neural lobe and suggest that the effect of enkephalins may be intimately related to calcium-sensitive neurosecretory events.
Animals↗
Arginine vasopressin release following surgical operations.
A study of plasma arginine vasopressin (AVP) concentrations in 16 patients undergoing uncomplicated cholecystectomy was carried out to determine the relative importance of the various stimuli to AVP secretion during and after an operation. Eight of the 16 patients were given a high epidural blockade from T4 and T12 and blood samples were taken before, at frequent intervals during and for two days after operation for determination of plasma AVP and osmolarity; systolic blood pressure was measured each time a blood sample was taken. In the 16 patients there was a 1.8-fold rise of plasma AVP after induction of anaesthesia (from 1.7 pmol/l median basal value to 13.1 pmol/l) and an 8.8-fold rise after skin incision, the highest concentration during operation being 102 pmol/l. There was no significant difference in AVP concentrations, urine volumes or plasma osmolality in the control and epidural groups. Systolic blood pressure fell in all patients during operation by between 14 and 54 per cent, the fall being significantly greater in the epidural group. Notwithstanding the evidence that certain nervous impulses do cause an increased secretion of AVP during operation, these results clearly show that in the absence of such stimuli there is still an increased secretion, almost certainly caused by a fall in the blood pressure.
Adult↗
Water and electrolyte composition of urine and ileal fluid and its relationship to renin and aldosterone during dietary sodium deprivation in patients with ileostomies.
1. The electrolyte and water composition of urine and ileal fluid was studied in six patients with ileostomies during dietary sodium deprivation and at the same time measurements were made of plasma renin activity, plasma aldosterone concentration, renal aldosterone excretion and plasma arginine vasopressin concentration. 2. In each subject there was a reduction in renal sodium excretion within 24 h of sodium deprivation. Significant rises in plasma renin activity, plasma aldosterone concentration and renal aldosterone excretion occurred by day 2 of sodium deprivation. 3. There was only modest conservation of sodium by the ileum during sodium deprivation, but ileal potassium concentration rose progressively. There were significant associations between ileal-fluid potassium concentration and plasma renin activity or renal aldosterone excretion. 4. Under the conditions of the experiment a diuresis was observed in each subject during dietary sodium deprivation. This did not appear to depend on changes in plasma arginine vasopressin concentration.
Adult↗
The effect of intracerebroventricular injections of morphine on vasopressin release in the rat.
1. An investigation was carried out to determine the effect of intracerebroventricular (I.C.V.) micro-injections of morphine on vasopressin (AVP) release in the urethane-anaesthetized rat. 2. Plasma AVP levels at different time intervals, following I.C.V. injection of 10-150 microgram morphine, were measured by radioimmunoassay. The effect of I.C.V. micro-injections of morphine on urine outflow was also studied in a group of water-loaded rats. 3. The vasopressin response to I.C.V. micro-injections of morphine was both dose- and time-dependent. High dose of 50 and 150 microgram morphine produced short latency stimulation of AVP release, followed by a fall. The low dose of 10 microgram morphine produced only a long latency inhibition. The most consistent response of I.C.V. injection of morphine was an inhibition of release. 4. Both stimulatory and inhibitory effects of morphine on vasopressin release were naloxone reversible and stereospecific. 5. I.C.V. micro-injections of morphine produced a dose-dependent rise in mean arterial blood pressure of short latency. Naloxone (0.5 mg/kg) completely abolished the rise seen with 10 microgram morphine and diminished the rise with 50 microgram. 6. Doses of 10 and 50 microgram morphine injected I.C.V. produced an immediate antidiuresis in water-loaded rats under urethane anaesthesia. 7. The vasopressin response to I.C.V. micro-injections of morphine is independent of the effects on the cardiovascular system and may involve different opiate receptor populations. The results also suggest the possibility that opiate receptors with different affinities for morphine may be responsible for the stimulatory and inhibitory effects of morphine on vasopressin release.
Animals↗
Inappropriate secretion of antidiuretic hormone in infants with respiratory infections.
Four infants in whom excessive secretion of antidiuretic hormone was associated with pulmonary infections are reported. Severe hyponatraemia was noted in 3 of them; in the fourth, fluid restriction may have prevented this complication.
Bronchiolitis, Viral↗
Variations in plasma concentrations of vasopressin during the menstrual cycle.
Plasma vasopressin concentrations, determined by radioimmunoassay, were followed throughout the menstrual cycle in eight healthy women. The concentrations were found to depend on the day of the menstrual cycle. The mean concentration on day 1 was 0.5 +/- 0.08 (S.E.M.) microunits/ml, while that on days 16-18 was 1.1 +/- 0.16 microunits/ml. These values were significantly (P less than 0.02) different. Vasopressin release in women may thus depend on the hormonal changes during the menstrual cycle.
Adult↗
Effects of prostaglandin inhibition on vasopressin levels in women with primary dysmenorrhea.
Arginine vasopressin (AVP) concentrations in plasma were studied in women with primary dysmenorrhea before and after treatment with naproxen, and in healthy control women on the first day of menstruation. In the treated group the AVP concentration was about 4 times higher than that in the controls, and the AVP level remained unchanged after almost complete pain relief had been obtained by treatment with the prostaglandin synthesis inhibitor. No significant differences were found between the 2 groups in plasma osmolality and sodium concentration on the first day of menstruation, or in the concentrations of progesterone and estradiol at this time or in the midluteal phase of the preceding menstrual cycle. These results indicate that increased secretion of AVP may play an etiologic role in dysmenorrhea, activating the uterus via a final step of prostaglandin synthesis an release.
Adult↗
The effect of cold exposure on fluid balance, circulating arginine vasopressin concentration and milk secretion in the goat.
Total body water, water intake, urine output, milk yield, plasma, milk and urine osmolality and plasma arginine vasopressin concentration were measured in goats exposed to thermoneutral (20 degrees C) and cold (0-1.0 degrees C) environments for 24 h. Cold exposure caused the animals to reduce their water intake substantially. This was accompanied by a decrease in total body water and an increase in osmolality of plasma and milk. The output of urine decreased as cold exposure progressed but free water clearance by the kidney was not significantly different in thermoneutral and cold environments and cold exposure had no effect on circulating arginine vasopressin concentration. Milk yield was reduced by cold exposure and it is suggested that the reduced net movement of water from blood to milk is partly a consequence of the dehydration induced by cold exposure and that this, in turn, is due primarily to a decrease in water intake with no effective renal compensation.
Animals↗
The effect of the methionine enkephalin analogue DAMME on the vasopression response to tilt in man.
1. Infusion of the methionine enkephalin analogue DAMME (Sandoz) inhibits the rise in plasma arginine vasopressin after a 65 degrees head-up tilt. 2. DAMME does not significantly affect the blood pressure, pulse rate or plasma volume changes produced by tilt.
Adult↗
Vasopressin concentrations in the neonatal period.
Vasopressin concentrations were measured in the cord blood of thirty infants, thirteen delivered vaginally and seventeen by Caesarean section. There was no correlation with maternal values but the concentration following vaginal delivery (13.5 microunits/ml +/- 7.9 SD) was significantly higher than that following Caesarean section (4.2 microunits/ml +/- 6.6 SD). Gestational age did not affect the concentrations, which fell during the first week of life and then rose gradually in term and pre-term infants. High levels were found in seven sick babies. There was no correlation in the first 3 weeks of life between plasma vasopressin and plasma or urine osmolality in well and sick babies.
Cesarean Section↗
Haemostatic effects of lysine vasopressin and triglycyl lysine vasopressin infusion in patients with cirrhosis.
Eight patients with cirrhosis were infused with lysine vasopressin (10 microgram LVP) and triglyclylysine vasopressin (750 microgram and 2000 microgram Glypressin, GVP) on separate occasions. LVP infusion resulted in an increase in factor VIII, factor VIII-related antigen and plasminogen activator (PA). The factor VIII antigen: activity ratio decreased following infusion, but factor VIII electrophoretic mobility and in vitro decay rate were unchanged. GVP infusion produced no change in factor VIII or PA. Assay of vasopressin-like antigen and antidiuretic activity showed that GVP is cleaved to LVP in vivo. The low levels of LVP formed by this reaction might explain the prolonged vasometer effects of GVP, as well as its inability to cause release of factor VIII or PA. Compared to LVP, GVP has a longer pressor effect in vivo, has no effect on fibronolysis and exhibits no cardiotoxic effects and may therefore be the treatment of choice in bleeding oesophageal varices.
Antigens↗
Release of oxytocin induced by salt loading and its influence on renal excretion in the male rat.
1. The present study investigates the nature and magnitude of the renal response to plasma levels of oxytocin which might be induced by salt loading. 2. Increased plasma osmolality induced by loading with NaCl is an effective stimulus for oxytocin release in the unanaesthetized male rat. Plasma oxytocin concentration was positively correlated (r = 0-.77) with plasma osmolality. Plasma oxytocin (muu./ml.) = 0.37 x (plasma osmolality (m-osmole/kg) -297). 3. In anaesthetized Long Evans rats intra-atrial administration of oxytocin at rates of 0.05 and 0.15 m-u./ml. produced plasma hormone concentrations (5 +/- 1 and 16 +/- 2 mum./ml. respectively) within the range induced by salt loading. 4. Oxytocin administration at 0.15 and 1.5 m-u./min in Long Evans rats produced dose-related increases in urine flow and Na+ and Cl- excretion. Renal responses to 0.05 m-u. oxytocin/min were equivocal. 5. Oxytocin administration at 0.15 m-u./min was ineffective in Brattleboro rats but 1.5 m-u./min led to increased Na+ and Cl- excretion and a reduction in urine flow. 6. Plasma oxytocin levels similar to those induced by severe dehydration or salt loading are effective in increasing renal Na+ and Cl- excretion and urine flow. These effects on water and electrolyte excretion appear to be independent of each other and both may be modified by the presence or absence of vasopressin. 7. This study provides no evidence for a major role for oxytocin in the day to day regulation of salt or water balance under conditions of normal hydration in the male rat.
Animals↗
Evidence for endogenous opioid control of vasopressin release in man.
The role of endogenous opioids in the control of vasopressin secretion was studied using the pure opiate antagonist naloxone. Naloxone both reduced resting levels of vasopressin and inhibited the rise in vasopressin induced by an orthostatic stimulus. These results suggest that endogenous opioids are important as a tonic stimulus to vasopressin release in man.
Adult↗