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M L Forsling

Publications and source records attributed to M L Forsling.

At least 55 records · Page 3Linked to original sources
PubMed1997

Arginine vasopressin increases renal sodium excretion in the anesthetized rat through V1 receptors.

We have previously suggested that the increase in renal Na+ excretion in response to physiological doses of arginine vasopressin (AVP) is not directly linked to the V2-mediated antidiuretic effect. In the present study we investigated the possible involvement of AVP V1 receptors in this natriuresis using a specific AVP V1 antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine arginine vasopressin, d(CH2)5[Tyr(Me)2]AVP, infused at a rate of 15 ng.min-1. Male anesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL.min-1. After a 3-h equilibration period, samples were collected at 20-min intervals for 4 h for the determination of urine flow, and Na+ and K+ excretion rates. In those animals in which the effects of AVP were studied, a 1-h control period was allowed following which AVP was infused at 0.02-0.08 pmol.min-1 for 1 h 20 min in separate groups of animals and then returned to the infusate alone for the last part of the experiment. In other groups the AVP V1 antagonist d(CH2)5[Tyr(Me)2]AVP (15 ng.min-1) alone or in combination with AVP (at various dose rates) was also administered for 1 h 20 min. All dose rates of AVP produced an antidiuresis which was associated significantly to increased Na+ excretion rate. However, AVP administration at the median dose rate (0.04 pmol.min-1) significantly (p < 0.01) decreased the amount of urine voided by comparison with control animals (6.34 +/- 1.05 ml vs. 11.892 +/- 0.03 mL, n = 7) although the urinary Na+ was elevated (967 +/- 18 mumol, vs. 742 +/- 81 mumol, n = 7). This AVP-induced increase in urinary Na+ loss was abolished in animals receiving combined AVP (0.04 pmol.min-1) and AVP V1 antagonist (674 +/- 47 mumol, n = 7) although the antidiuretic effect persisted. Urine flow and Na+ excretion rates remained unchanged in groups of animals administered AVP V1 antagonist alone. In all groups, the K+ excretion rates did not significantly differ. It is concluded that the V1 receptor mediates the natriuretic effect of AVP.

Anesthesia↗
PubMed1996

Diurnal variation in the effect of melatonin on neurohypophysial hormone release from the rat hypothalamus.

Secretion of neurohypophysial hormones can show a diurnal variation. This has been investigated further in rats maintained on 14 h light:10 h dark using a previously validated in vitro technique employing hypothalami obtained at three different times, 2-3 h after lights on (group A), 13-14 h after lights on (group B), and at 4-5 h after lights off (group C). Hormone release under basal conditions and following stimulation with 40 mM KCl was monitored with or without added melatonin in the concentration range 4.3-43 nM. Basal release of hormone was not influenced by the time of day when the animals were taken, although stimulated release was elevated at midnight. In groups A and B both doses of melatonin significantly reduced basal and stimulated release of vasopressin and basal release of oxytocin (p < 0.01), although no effect was seen in group C animals. Inhibition of stimulated oxytocin release was only produced in group B. These findings suggest that the inhibitory effect of melatonin depends on the time of day and are consistent with the suggestion that melatonin secretion during the dark period may acutely downregulate binding sites in the brain.

Animals↗
PubMed1996

Oxytocin release is inhibited by the generation of carbon monoxide from the rat hypothalamus--further evidence for carbon monoxide as a neuromodulator.

Recent evidence suggests that the gas nitric oxide can modulate the secretion of a number of hypothalamic hormones, and may be co-localized particularly to oxytocin-containing neurons. Another gas, carbon monoxide (CO), has also been suggested to play a role in neural signaling in the brain, and the synthetic enzyme responsible for the generation of carbon monoxide has been reported to be present in the rat hypothalamus. In this study, we have therefore investigated whether CO has the ability to modify the release of oxytocin from acute rat hypothalamic explants. Hemin, a specific CO precursor through the enzyme heme oxygenase (the enzymatic pathway synthesizing endogenous CO, was found to inhibit KCl-stimulated oxytocin release, with a maximal effect at 10(-5) M, while showing no effect on basal oxytocin secretion. The stimulation of oxytocin by serotonin 10 ng/ml was also significantly antagonized by hemin 10(-7) M. An inhibitor of heme oxygenase, zinc-protoporphyrin-9, had no effect on basal or stimulated oxytocin release. When hemin and zinc-protoporphyrin-9 were given together, the hemin-induced inhibition of oxytocin was completely antagonized by the enzyme inhibitor. Ferrous hemoglobin A0, a substance known to bind CO with high affinity, had no effect on either basal or stimulated oxytocin release, but when hemin and ferrous hemoglobin A0 were given together the hemin-induced inhibition of oxytocin was completely blocked. These findings provide evidence that endogenous CO may play a role in the control of oxytocin release and that, by analogy with nitric oxide, CO may represent a major new neuroendocrine modulator.

Animals↗
PubMed1996

The effect of oophorectomy and hormone replacement on neurohypophyseal hormone secretion in women.

OBJECTIVE: There is evidence to suggest that the release of neurohypophyseal hormones may be influenced by the circulating concentrations of gonadal steroids. We therefore monitored this relationship in women undergoing prophylactic bilateral oophorectomy at the time of hysterectomy with subsequent hormone replacement therapy and compared it with that in women undergoing hysterectomy with conservation of ovaries. DESIGN: Patients were randomly allocated to receive either transdermal oestradiol patches, 0.05 mg/day, or subdermal implants containing either 50 mg oestradiol or 50 mg oestradiol with 100 mg testosterone. Blood samples for determination of plasma hormone concentrations, electrolytes and osmolality were obtained immediately before and after surgery and then at two-monthly intervals for 8 months and finally at 12 months. MEASUREMENTS: Free oestradiol, vasopressin and oxytocin were measured by radioimmunoassay. RESULTS: Vasopressin concentrations were found to fall after surgery in oophorectomized women, but not in those with ovaries. There were no changes in fluid balance to account for the reduced plasma vasopressin concentrations. During treatment oestradiol appeared to enhance and testosterone to suppress vasopressin release. Oophorectomy had no significant effect on plasma oxytocin concentrations, but in the groups receiving oestradiol implants concentrations fell significantly at 8 and 12 months compared with the value at 6 days. CONCLUSION: The observed changes in plasma vasopressin concentrations were consistent with the observations in experimental animals and provide evidence that vasopressin release in the human is influenced by gonadal steroids.

Adult↗
PubMed1996

The effect of pinealectomy on osmotically stimulated vasopressin and oxytocin release and Fos protein production within the hypothalamus of the rat.

Osmotically stimulated vasopressin and oxytocin release were measured in pinealectomized and sham operated male rats infused with hypertonic sodium chloride. Neuronal activation in the hypothalamic regions associated with oxytocin and vasopressin release was investigated by quantitative assessment of Fos protein production. The osmotically stimulated release of both vasopressin and oxytocin was significantly lower in pinealectomized animals as compared to sham operated controls. The slope of regression lines between plasma osmolality and hormone concentrations in the sham animals showed a 1.0 +/- 0.1 pmol per mosm/kg rise in vasopressin and 2.0 +/- 0.4 pmol per mosm/kg rise in oxytocin whilst in the pinealectomized animals these values were significantly lower at 0.4 +/- 0.1 pmol vasopressin per mosm/kg and 0.8 +/- 0.2pmol oxytocin per mosm/kg. The osmotic thresholds for hormone release were unaffected by pinealectomy. Fos production was also significantly lower in the supraoptic nucleus and organ vasculosum of the lamina terminalis in the pinealectomized rat at 62 +/- 20 and 59 +/- 9 Fos immunoreactive cells/section as compared to corresponding values of 202 +/- 31 and 123 +/- 20 Fos immunoreactive cells/section in the shams. These observations suggest that reduced hormone release in the pinealectomized animal is due to lowered responsiveness of central osmoregulatory mechanisms and that melatonin may therefore influence the activation of the magnocellular system.

Animals↗
PubMed1996

Arginine vasopressin mediates the chloroquine induced increase in renal sodium excretion.

We postulated that chloroquine increases plasma arginine vasopressin (AVP) concentrations thus altering renal Na+ clearance. Therefore, we studied a relationship between plasma AVP concentrations and urinary Na+ output in separate groups of Sprague-Dawley (SD) rats administered chloroquine (3 micrograms/min) for 1 h 20 min. We also monitored Na+ excretion rates in Brattleboro AVP-deficient Di rats challenged with hypotonic saline load and administered chloroquine for 1 h 20 min. To establish whether chloroquine-induced changes in renal Na+ excretion were mediated via AVP V1 receptors, we studied Na+ excretion rates in groups of SD rats administered chloroquine or AVP in the presence of AVP V1 receptor antagonist (1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-2-O-methyltyrosine arginine vasopressin (d(CH2)5(Tyr(Me)2) AVP) at 11 pmol/min for 1 h 20 min. The Na+ excretion rate rose significantly (P < 0.01) from a pretreatment level of 9.8 +/- 1.0 mumol/min to a peak of 14.1 +/- 0.9 mumol/min in SD rats (n = 7) administered chloroquine. The Na+ excretion rate remained unaltered around 8.5 mumol/min in rats simultaneously administered chloroquine and the AVP V1 receptor antagonist. This compared with control rats (8.1 +/- 0.5 mumol/min, n = 7) and animals administered AVP V1 receptor antagonist alone (8.7 +/- 0.6 mumol/min, n = 7). Chloroquine did not affect urine flow, Na+ or K+ excretion rates in Brattleboro AVP-deficient Di rats. Administration of AVP alone was associated with significant increases in renal Na+ excretion rate. Blockade of AVP V1 receptors abolished the AVP-dependent increase in urinary Na+ loss. We conclude that at least part of the chloroquine-induced increase in Na+ excretion is mediated by chloroquine stimulating an increase in plasma AVP concentration.

Aldosterone↗
PubMed1996

Release of vasopressin in response to altered plasma volume and sodium concentrations following pinealectomy in the rat.

Pinealectomy has been shown to alter daily rhythms of neurohypophysial hormone release, with plasma hormone concentrations being elevated in the morning, as compared to intact rats. To determine whether pineal removal also altered the response to known stimuli of hormone release, vasopressin concentrations were measured in control, sham-operated, and pinealectomized animals during extracellular fluid hypertonicity produced by an intraperitoneal (i.p.) injection of hypertonic saline or hypovolaemia produced by an i.p. injections of polyethylene glycol. In the combined sham-operated and unoperated groups, injection of hypertonic saline produced a marked increase in plasma vasopressin concentrations from 2.18 +/- 0.28 to 7.2 +/- 1.24 pmol/liter, but the response was attenuated in pinealectomized animals, concentrations increasing to only 3.4 +/- 1.2 pmol/liter. Similarly, following infusion of hypertonic saline, the increase in plasma vasopressin per unit increase in plasma sodium was lower in pinealectomized animals than the pineal intact controls. The response to hypovolaemia was also attenuated, plasma hormone concentrations following reduction in blood volume of approximately 10% increasing to only 3.6 +/- 0.6 pmol/liter as compared to 7.3 +/- 2.2 pmol/liter in the control groups. There were no significant differences in pituitary vasopressin content in any of the groups studied. Thus, the pineal may influence the vasopressin response to physiological stimuli.

Animals↗
PubMed1996

The natriuretic actions of vasopressin in the female rat: variations during the 4 days of the oestrous cycle.

The renal actions of vasopressin were studied in the conscious female rat. Vasopressin caused a dose-dependent increase in sodium excretion when administered at 40-160 pmol/min. The highest dose, which increased sodium excretion from 10.4 +/- 0.3 mumol/min (n = 32) to 18.3 +/- 0.8 mumol/min (n = 8, P < 0.001), also caused a significant rise in glomerular filtration rate (GFR). The antidiuretic and natriuretic responses to vasopressin varied significantly over the 4 days of the oestrous cycle. Both responses were greatest on pro-oestrus, being -57 +/- 3 and 52 +/- 3% above the control values with 80 pmol vasopressin/min. Responses of similar magnitude were also seen on dioestrus day 1. On these two cycle days the effects on urine flow and sodium excretion were accompanied by a significant increase in GFR. Smaller antidiuretic and natriuretic responses were seen on oestrus and dioestrus day 2, without concomitant changes in GFR. As the plasma vasopressin concentrations produced by hormone infusion were similar on each day of the cycle, the renal responsiveness to vasopressin appears to vary over the 4 days of the oestrous cycle. This may be important in terms of alteration and possible disturbances of fluid balance which may occur during reproductive cycles and pregnancy.

Animals↗
PubMed1995

Diurnal variation of the pituitary-adrenal and AVP responses to stress in rats under food restriction.

In the present study plasma corticosterone (B), ACTH and vasopressin (AVP) were determined in 2 groups of Wistar rats, a control group (C) with free access to food, and a food restricted group (FR) with access to food only from 0900 to 1100 h for 14 days. Blood samples were collected by decapitation under unstressed (basal) conditions and immediately after 30 minutes of immobilization stress applied at AM (0800 h) and at PM (2000 h). The basal plasma B concentrations in C group presented diurnal variation with higher values at PM than at AM. The restricted feeding regimen resulted in a 12 hour shift of peak B values. Basal plasma ACTH rhythm in group C is parallel to diurnal B variation, attaining higher levels at PM. Rats under food restriction presented higher basal plasma ACTH levels at AM than C group, however there was no AM-PM difference. In both groups after stress plasma B concentrations increased in comparison to those in the unstressed rats. There was no significant AM-PM difference in the absolute B values attained in C or FR groups. The stress-evoked ACTH response was higher at AM than at PM in group C. In the FR group the ACTH response was similar in the morning and evening, although the ACTH concentrations achieved in the morning was lower than in group C. Basal plasma AVP levels were similar at AM and PM in both C and FR groups. Immobilization stress evoked no plasma AVP response in neither groups. Our results indicate that long term food restriction is able to modify the diurnal rhythms of both basal secretion and stress responsiveness of pituitary-adrenal axis by an as yet uncharacterized mechanism.

Adrenocorticotropic Hormone↗
PubMed1995

Hyperthermic and endocrine effects of intravenous prostaglandin administration in the pig.

Experimentally induced fever is accompanied by a variety of hormonal changes, and there is evidence to suggest that some of these responses may be mediated by prostaglandins. However, little is known about the endocrine effects of peripherally administered prostaglandins, especially in domesticated species. In this study, the effects of intravenous prostaglandin E2 (PGE2; 20 micrograms/kg) on deep body temperature and plasma concentrations of cortisol, lysine vasopressin (LVP), and growth hormone were investigated in prepubertal pigs (n = 6) prepared with venous catheters and sampled at 10-min intervals for 3 hr. PGE2-induced hyperthermia, which lasted for the duration of the study, was accompanied by a 70-min increase in cortisol and LVP concentrations. Moreover, this hyperthermic response was checked when LVP levels were high. These results indicate that a fever-inducing intravenous injection of PGE2 produced a marked anterior and posterior pituitary hormone response in growing pigs. Also, the transient increase in LVP may be correlated with a central action of the hormone, limiting the extent of the fever. In addition, because the majority of the animals exhibited mild hyperthermia (0.5 degrees C) under control conditions, the results suggest that, in a given population of pigs, there may be some animals that exhibit stress-induced hyperthermia.

Animals↗
PubMed1995

Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig.

Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but no change in adrenaline or noradrenaline levels was observed. All these effects were prevented or attenuated when the animals were pretreated intravenously with the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal expression of c-Fos were observed in hypothalamic regions concerned with thermoregulation, neurohypophysial secretion, and the control of pituitary-adrenocortical function. The stimulatory action of LPS in the median preoptic, supraoptic and paraventricular nuclei was prevented by IND, whereas IND given alone was without effect. These findings suggest that inducible cyclo-oxygenase pathways are responsible for the febrile and neuroendocrine effects of endotoxin in this species.

Animals↗
PubMed1995

Do vasopressin and oxytocin have synergistic renal effects in the conscious rat?

The renal effects of arginine vasopressin and oxytocin were studied in the conscious unrestrained rat infused with 0.077 M NaCl. Peptides were infused at rates of 24 and 160 pmol/min (vasopressin) or 30 and 200 pmol/min (oxytocin) either alone or as a combination of the two lower or two higher doses. The rates of infusion were selected to give ratios of oxytocin:vasopressin similar to those seen in the plasma of euhydrated and dehydrated rats. Vasopressin produced dose-dependent antidiuretic and natriuretic responses, the natriuresis commencing after 15-30 min infusion. Oxytocin produced dose-dependent diuretic and natriuretic responses, the natriuresis commencing within the first 15 min of infusion. Combined infusion of vasopressin and oxytocin produced dose-dependent antidiuretic responses which were comparable to those seen with vasopressin alone. The natriuretic response from combined infusion at the higher rate appeared to have the greater magnitude for individual 15-min periods of the vasopressin response combined with the longer duration of the oxytocin response. Although the total natriuretic response was therefore greater, this difference failed to reach significance. Only the higher rates of infusion of vasopressin and oxytocin significantly increased the clearance of sodium, by 53 +/- 23 and 62 +/- 18% and glomerular filtration rate (GFR) by 23 +/- 4 and 23 +/- 4% respectively. The clearance of sodium during the combined hormone infusion was significantly greater (109 +/- 21%), while the rise in GFR at 23 +/- 5% was comparable to that seen when each hormone was given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Changes in neuronal metabolism in hypothalamic periventricular regions following acute alteration of cerebrospinal fluid composition in conscious rats.

Quantitative 2-deoxyglucose (2-DG) autoradiography was employed to determine the effect of elevating cerebrospinal fluid osmolality on neuronal metabolism of hypothalamic periventricular regions in conscious rats. Injection of hypertonic mannitol solution into the dorsal third ventricle had no significant effect on local cerebral glucose utilization, whereas administration into the ventral third ventricle resulted in a significant elevation in 2-DG uptake in only the posterior pituitary, median preoptic nucleus (MnPo), median eminence and suprachiasmatic nucleus. These results indicate the contribution of a synaptic connection in the MnPo in the activation of the osmoreceptor complex.

Animals↗
PubMed1994

The CCKA receptor antagonist devazepide inhibits the effect of apomorphine on vasopressin release in pigs.

1. A transient increase in plasma vasopressin concentrations represents a physiological correlate of nausea in animals that vomit. 2. The CCKA receptor antagonist devazepide has previously been shown to inhibit vasopressin release induced in pigs by intravenous (i.v.) CCK. 3. This study investigated whether devazepide (70 micrograms/kg i.v.) would affect vasopressin secretion induced in pigs (n = 6) by the emetic drug apomorphine (25 micrograms/kg i.v.). 4. Apomorphine stimulated vasopressin release in the 30 min period following injection; this effect was prevented by prior administration of devazepide. 5. The results suggest that CCKA receptor antagonists may have the ability to prevent nausea and/or emesis.

Animals↗
PubMed1994

Colchicine injected into the anterior forebrain in rats decreases blood pressure without changing the responses to haemorrhage.

In a previous publication rats were shown to develop a marked positive sodium balance 6 days after injection of 1 microgram colchicine into their anterior forebrains. This was thought to be the normal hydromineral balance response to correct an hypothesised colchicine-induced decrease in blood volume (and/or pressure). To test this hypothesis, fluid and sodium intakes and excretion were measured before and then for 6 days following injection of colchicine (1 microgram in 250 nl) into the anterior forebrain, around the diagonal band of Broca, in male Wistar rats. At the end of the 6 days the animals were anaesthetised with urethane and blood pressure measured continuously before during and after a 3.5 ml haemorrhage. Blood pressure was significantly reduced (86.4 +/- 3.9 n = 11 vs. 67.7 +/- 3.4 mm Hg n = 12, p < 0.01) in the colchicine-treated rats compared to the controls and failed to recover following the haemorrhage. Measured blood parameters were similar in both colchicine-treated and nontreated groups, including plasma levels of vasopressin both before and following the haemorrhage. These results suggest that the colchicine injections may have compromised a central component of the sympathetic nervous system, thereby leading to the significant decrease in blood pressure without compensatory vasopressin release, and the lack of recovery of the decrease in blood pressure following a haemorrhage.

Animals↗
PubMed1994

Interleukin-1 beta and interleukin-6 stimulate neurohypophysial hormone release in vitro.

Interleukin-1 (IL-1) and interleukin-6 (IL-6) have been reported to stimulate the release of corticotrophin-releasing hormone (CRH) in vitro, the response being antagonized by the cyclo-oxygenase inhibitor, indomethacin. The effects of cytokines on the other major ACTH-releasing hormone, vasopressin (AVP), and the other neurohypophysial hormone, oxytocin, have been little studied, and the published data are conflicting. We have therefore used a previously validated rat hypothalamic explant model to evaluate whether IL-1 beta and IL-6 can directly activate the AVP and oxytocin neurosecretory system. In addition, we have also investigated the effects of inhibition of cyclo-oxygenase (CO) and lipoxygenase (LO) activities on the stimulated release of AVP and oxytocin by means of a series of antagonists, including a specific LO pathway inhibitor. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubations, and estimation of AVP and oxytocin concentrations in the medium by specific and sensitive radioimmunoassays. It was found that IL-1 beta produced a dose-dependent increase in the release of AVP and oxytocin at doses of 10 and 100 U/ml (P < 0.005). Only at the higher dose of 100 U/ml was IL-6 able to increase significantly AVP and oxytocin release (P < 0.05). These stimulatory effects of IL-1 beta and IL-6 were blocked by cyclo-oxygenase inhibitors, indomethacin (28 microM) and ibuprofen (100 nM), but not by the lipoxygenase inhibitor, BW A4C (10 micrograms/ml), suggesting that prostaglandins are involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗