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M L Forsling

Publications and source records attributed to M L Forsling.

At least 73 records · Page 4Linked to original sources
PubMed1994

Interaction of aldosterone and oxytocin to influence renal sodium excretion in rats.

The possibility of an interaction between oxytocin and aldosterone to influence renal Na+ excretion was investigated in Inactin-anaesthetized male Sprague-Dawley rats. Endogenous plasma concentrations of aldosterone were suppressed by either adrenalectomy or bicarbonate infusion. The effects of 2 h intravenous administration of oxytocin (0.04 pmol/min) and/or aldosterone (42 pmol/min) on renal Na+ handling were studied in 0.077 M NaCl-infused adrenalectomized (Adx) rats and groups of intact animals that were infused with 0.077 M NaHCO3. Aldosterone alone significantly (P < 0.01) reduced Na+ excretion from pretreatment peak value of 5.0 +/- 1.0 to 1.5 +/- 0.4 mumol/min in Adx animals (n = 8) and 9.2 +/- 1.2 to 5.2 +/- 1.2 mumol/min in NaHCO3-infused rats (n = 8) by 2 h after the start of administration. However, combined administration of aldosterone and oxytocin was associated with a significantly (P < 0.01) increased Na+ excretion rate from a peak pretreatment value of 6.8 +/- 0.7 mumol/min to a peak value of 11.5 +/- 1.1 mumol/min by 1 h 40 min after the start of treatment in Adx rats (n = 7). In bicarbonate-infused rats (n = 8) Na+ excretion rose within 20 min of the start of treatment from a pretreatment peak of 9.0 +/- 0.8 mumol/min to a peak value of 13.5 +/- 0.8 mumol/min in response to combined hormone administration. In conclusion, we have shown that concomitant administration of aldosterone and oxytocin increased the rate of excretion of Na+ in two different preparations, which supports the idea of an interaction between the steroid and oxytocin to promote Na+ loss.

Adrenalectomy↗
PubMed1994

The effect of vasopressin and oxytocin on glomerular filtration rate in the conscious rat: contribution to the natriuretic response.

Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were determined in the conscious unrestrained rat infused with hypotonic saline. The effects of vasopressin infused at 24 and 160 pmol/min and oxytocin infused at 30 and 200 pmol/min were determined. The lower doses of each hormone gave plasma concentrations within the physiological range whereas the higher doses produced plasma concentrations equivalent to those seen following dehydration. Vasopressin produced dose-dependent antidiuretic and natriuretic responses. Hormone infused at both rates increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. Fractional excretion of sodium was significantly elevated by both doses. Oxytocin produced dose-dependent diuretic and natriuretic responses. Again both rates of infusion increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. The lower dose caused a significant increase in the fractional excretion of sodium. It appears, therefore, that increases in GFR may have a role in the natriuretic response to both hormones. However, this response can also be seen when GFR remains unchanged. This fact, together with the observed increases in the fractional excretion of sodium, indicates that these hormones have additional tubular actions.

Animals↗
PubMed1993

Neurohypophysial hormones and circadian rhythm.

In conclusion, neurohypophysial hormone levels in human plasma and in the plasma, pituitary, and hypothalamus of the rat show clear rhythms over the 24-hour period. These are not true circadian rhythms, as they may be modified by a number of factors, including the stage of the estrous cycle and hydrational status. There is evidence to suggest that the patterns observed may in part reflect the action of the pineal product melatonin. Pinealectomy influences the pattern of hormone release, while melatonin and its analogues inhibit hormone release, although the major circulating metabolite has no effect.

Animals↗
PubMed1993

Hyperactivity of the hypothalamo-pituitary-adrenal axis in obesity: a study of ACTH, AVP, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia.

OBJECTIVE: The purpose of this study was to determine whether alterations in the hypothalamo-pituitary-adrenal axis and arginine vasopressin secretion, which have been associated with animal obesity, also occur in man. DESIGN: Cross-sectional analysis of extremely obese women and normal weight controls. PATIENTS: Thirty-three obese premenopausal, non-diabetic women (mean age 31 years, mean body mass index (BMI) 41), and 15 normal weight controls (mean age 24 years, mean BMI 22). MEASUREMENTS AND RESULTS: Arginine vasopressin (AVP), ACTH, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia (0.2 units Actrapid/kg body weight for obese; 0.15 unit/kg for controls) were measured. The obese women were further characterized by anthropometric measurements (weight, body mass index, fat distribution) and indices of insulin secretion/resistance: fasting insulin, insulin secretion during 75-g oral glucose tolerance test area under curve, insulin-stimulated glucose disposal and an index of insulin resistance. No significant differences were found in the basal levels of ACTH, AVP, beta-lipotrophin or cortisol. An augmented peak beta-LPH (n = 16, P < 0.02, the difference of the mean 3.65, 95% confidence interval 1.33-10) and ACTH (n = 16, P = 0.05, the difference of the mean 2.12, 95% CI 1.0-4.5) response were found in obese as compared with normal weight controls. Both ACTH and AVP areas under the curve were similar in both groups studied. There was additionally a direct positive association between the integrated ACTH response (area under the curve) and the weight of the obese subjects (P < 0.05, r2 = 0.265). The cortisol response was negatively correlated with insulin-stimulated glucose disposal (P < 0.01, r2 = 0.23), but not with other indices of insulin secretion/resistance (fasting insulin, oral glucose tolerance test area under the curve, index of insulin resistance) or fat distribution. Comparable responses to hypoglycaemia were seen for AVP and cortisol. There was no correlation between the ACTH, AVP or cortisol responses. CONCLUSION: Obesity is associated with increased activity of the hypothalamo-pituitary-adrenal axis as supported by augmented ACTH and beta-lipotrophin secretion in response to insulin-induced hypoglycaemia and the positive association between the ACTH response and the body weight of obese women studied.

Adrenocorticotropic Hormone↗
PubMed1993

The role of the pineal in the control of the daily patterns of neurohypophysial hormone secretion.

Plasma concentrations of neurohypophysial hormones show clear rhythms over 24 hr which can be suppressed by exposure to constant light, an observation consistent with pineal involvement. A study has therefore been performed on the changes in the hormone levels in the hypothalamus, posterior pituitary, and plasma over 24 hr in control, pinealectomised, and sham pinealectomised animals to determine if the pineal could play a role. Water intake, urine excretion, packed cell volume, plasma osmolality, and electrolytes were also monitored. Pinealectomy had little effect on fluid balance, but after 8 weeks for oxytocin and 2 weeks for vasopressin the morning values (0700-0800) for the circulating concentrations of the hormones were significantly higher in the pinealectomized group compared with the combined sham operated and unoperated groups (pineal intact). By contrast, the pituitary vasopressin was significantly lower in the pinealectomised group. The increase in plasma oxytocin and vasopressin seen over the hours of daylight and accompanying fall in plasma osmolality seen in the pineal intact group were absent in the pinealectomised group. Similarly, the evening fall in pituitary hormone concentrations and increase in hypothalamic hormone content were absent in the pinealectomised animals. After 10 days of exposure to constant light, the fall in plasma osmolality in the pineal-intact animals over the day was no longer significant; instead a significant increase in plasma osmolality and sodium was seen in the pinealectomised group. Exposure to constant light, while altering the patterns of neurohypophysial activity in the pineal intact group, had little effect on the pinealectomised animals.

Animals↗
PubMed1993

Melatonin and its analogs inhibit the basal and stimulated release of hypothalamic vasopressin and oxytocin in vitro.

The secretion of neurohypophyseal hormone and ACTH in the rat has been shown to exhibit circadian rhythms, with high values during the day and low values throughout the night. The neurohypophyseal hormone daily rhythm is altered by exposure to constant light and by pinealectomy. It was, thus, proposed that the observed fall in vasopressin (AVP), oxytocin, and ACTH over the hours of darkness could be related to the release of melatonin seen at this time. Therefore, a study was performed to determine the effect of melatonin on AVP, oxytocin, and CRH-41 release from the isolated rat hypothalamus in vitro. Employing a previously validated technique, rat hypothalami were incubated in either medium alone or medium containing melatonin or one of two melatonin analogs. Hormone release was measured by RIA, and the ratios were calculated and compared by Student's t test, with Dunnett's correction for multiple comparisons. Melatonin showed a dose-dependent inhibition of both basal and stimulated AVP and oxytocin release in the concentration range 4.3 x 10(-10) to 2.5 x 10(-3) M, while having no significant effect on the release of CRH-41. The two melatonin analogs, 2-iodomelatonin and 5-methoxy-N-isobutanoyltryptamine, were also found to inhibit both basal AVP and oxytocin release, indicating that this effect probably depends upon the presence of melatonin receptors in the hypothalamus. This inhibitory modulation of AVP, in the absence of any effect on CRH-41, suggests that melatonin may affect water balance by means of directly inhibiting hypothalamic AVP release. Furthermore, circadian rhythmicity in pituitary-adrenal activity may depend on melatonin modulation of AVP, rather than changes in CRH-41.

Animals↗
PubMed1993

Nitric oxide modulates the release of vasopressin from rat hypothalamic explants.

The enzyme nitric oxide (NO) synthase is present in the paraventricular nucleus, while nitric oxide has recently been shown to inhibit the stimulated release of corticotrophin-releasing hormone (CRH) in vitro. Thus the possible role of NO in regulating, vasopressin (AVP), which also plays an important role in pituitary-adrenal activity, has been investigated. The effects were studied of the NO donors, L-arginine, syndnonimine-1 (SIN-1) and sodium nitroprusside, on both the basal and stimulated release of AVP, employing a previously validated system. Rat hypothalami were incubated in either medium alone or medium containing the test substances and hormone release was measured by RIA. The effect of L-arginine in the presence of the NO synthase inhibitor, L-NMMA, was also investigated. L-arginine reduced KCl-evoked AVP release; this effect was reversed by L-NMMA and reduced by the addition of ferrous human Hb. Similarly, SIN-1 and sodium nitroprusside attenuated KCl-evoked AVP release. L-arginine also reduced IL-1 beta-stimulated AVP release. NO appears to directly and specifically inhibit the stimulated release of AVP from rat hypothalamic explants in vitro, similar to its effects on CRH. These findings provide further evidence that NO may be involved in neuroendocrine regulation.

Amino Acid Oxidoreductases↗
PubMed1993

Inter-colony variation in fluid balance and its relationship to vasopressin secretion in male Sprague-Dawley rats.

Salt and water balance and vasopressin secretion were measured in three colonies of Sprague-Dawley rats. Although sodium and water retention were similar between the groups, there were marked differences in both the rate and diurnal pattern of intake and excretion. Animals housed under semi-barrier conditions showed a lower basal plasma vasopressin concentration but were more sensitive to physiological stimuli. However, since pathogenic status and environmental conditions cannot entirely explain these results, genetic variation is likely to be a contributory factor.

Animal Husbandry↗
PubMed1993

Variations in oxytocin secretion during the 4-day oestrous cycle of the rat.

Oxytocin concentrations in the plasma, pituitary and hypothalamus of female rats were determined in the morning and evening over the 4-day oestrous cycle. Vasopressin concentrations were also determined to allow calculation of the ratios of the two hormones. The results were compared with those from male rats. Plasma oxytocin concentrations were significantly higher in the evening than in the morning on the day of oestrus. Although the evening concentration achieved was similar on each day of the cycle, morning plasma oxytocin concentrations showed a progressive rise from oestrus to pro-oestrus so that no significant diurnal increases were observed on the other days of the cycle. Vasopressin concentrations in the plasma were also seen to increase over the days of oestrus, dioestrus day 1 and dioestrus day 2. On pro-oestrus the plasma concentrations of vasopressin remained unchanged. The ratio of oxytocin:vasopressin fell during the light hours of the cycle. The hypothalamic content of both hormones showed a rise during the hours of daylight parallel to that seen in the plasma, whereas the pituitary content fell over the same period. The diurnal pattern of hormone release observed in male rats was similar to that in females at oestrus. However, the plasma oxytocin concentrations were significantly higher in the male. The plasma clearance rate of vasopressin did not vary significantly during the oestrous cycle. However, the plasma clearance rate for oxytocin did show significant variation, being highest on dioestrus day 1 and lowest on dioestrus day 2.

Animals↗
PubMed1993

Patterns of neurohypophysial hormone release during dehydration in the rat.

A study was performed investigating the daily patterns of hormone release accompanying changes in fluid balance in the male rat during 48 h of dehydration. The blood volume decreased by 18%, the largest change occurring during the initial period when the rats showed an effective loss of body sodium. During the second day of dehydration, sodium retention was again seen. Plasma sodium concentrations showed a progressive increase, the total rise being 5-6%; the greatest changes were seen during the dark phases of the cycle which may be due to the nocturnal food intake. Plasma vasopressin and oxytocin concentrations were significantly elevated throughout dehydration to levels which could be reproduced by acutely increasing plasma sodium and decreasing blood volume to the same extent. The observed increases were influenced by the phase of the day-night cycle, being greatest over the dark phases of the cycle. The overall increases were greatest when dehydration commenced at the start of the dark phase. Dehydration initially led to a rise in plasma corticosterone concentrations, whilst plasma concentrations of atrial natriuretic peptide were decreased. Plasma angiotensin II concentrations rose significantly during the later period of sodium retention.

Angiotensin II↗
PubMed1992

The effects of intravenous administration of cholecystokinin on feeding behaviour and release of pituitary hormones in pigs are not mediated by serotonergic (5-HT3) receptors.

Two experiments were carried out using the serotonergic (5-HT3) antagonist ondansetron (GR 38032F) to investigate whether the actions of peripherally-administered cholecystokinin octapeptide (CCK) in the prepubertal pig might involve 5-HT3 receptors. In Experiment 1, it was shown that ondansetron (10 or 30 mg, i.v.) did not affect the initial feeding response and did not modify the behavioural inhibition induced by a subsequent injection of CCK (1.3 microgram/kg, i.v.). In Experiment 2, it was demonstrated that the nauseogenic action of CCK, indicated by its stimulatory effect on release of vasopressin and cortisol, was not markedly altered by ondansetron (30 mg, i.v.). These results suggest that 5-HT3 receptors play a negligible part in mediating the behavioural and endocrine responses induced by bolus intravenous injections of CCK in this species.

Animals↗
PubMed1992

Regional expression of c-fos antigen in the basal forebrain following intraventricular infusions of angiotensin and its modulation by drinking either water or saline.

The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-min survival period modified this pattern of response. c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 min, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels. These experiments show that angiotensin II induces highly localized expression of c-fos in areas known to be concerned with the dipsogenic and endocrine actions of this peptide, and that this pattern is selectively altered by allowing the animal to drink solutions of different tonicity. Immediate-early gene expression is a novel and valuable method of determining the neural response to peptides at the cellular level.

Angiotensin II↗
PubMed1992

CCK-A receptors mediate the effect of cholecystokinin on vasopressin but not on cortisol in pigs.

Bolus intravenous injections of cholecystokinin (CCK) octapeptide induce a rapid rise in plasma vasopressin and a later increase in cortisol in the prepubertal pig. To determine whether these endocrine responses involve CCK-A or CCK-B receptors, this experiment investigated the effect of CCK (1 microgram/kg) in pigs (n = 7) pretreated with the CCK-A antagonist L 364718 (70 microgram/kg) or the CCK-B antagonist L 365260 (10 ng/kg and 10 micrograms/kg). The animals were prepared with jugular vein catheters and given the antagonist vehicle, L 364718, or L 365260 10 min before administration of CCK or saline. Analysis of hormone concentrations in blood samples taken 2, 5, 10, and 20 min after the second injection indicated that an abrupt rise in vasopressin, detectable within 2 min of CCK administration, occurred after vehicle or L 365260 pretreatment but not when CCK was preceded by L 364718. In contrast, the rise in plasma cortisol that was observed approximately 15 min after CCK injection was not prevented by either antagonist. Thus peripherally administered CCK induces vasopressin release by CCK-A receptor activation, in agreement with its inhibitory effect on food intake in this species. However, the effect of CCK on cortisol secretion does not appear to involve either CCK-A or CCK-B receptors.

Animals↗
PubMed1992

Differential effects of neuroexcitatory amino acids on corticotropin-releasing hormone-41 and vasopressin release from rat hypothalamic explants.

We have investigated the direct effects of different neuroexcitatory amino acids (EAA) on the secretion of CRH-41 and arginine vasopressin (AVP) from the rat hypothalamus maintained in vitro. CRH-41 and AVP released in the medium were assayed by RIA before and after incubation with N-methyl-D-aspartate (NMDA), N-methyl-D,L-aspartic acid, kainate (KA), and quisqualate in the concentration range 1 nM to 1 mM in either the absence or the presence of 1 mM Mg2+ in the medium. In the case of NMDA, the effect of the addition of glycine (1 and 10 microM) to the incubation medium was also studied. Finally, we investigated whether different periods of exposure (up to 100 min) of hypothalamic explants to NMDA and KA would affect CRH-41 release. While no EAA was able to induce CRH-41 release under any of the above conditions, 20-min incubations with NMDA in the dose range of 1 nM to 1 mM in the absence of added Mg2+ significantly stimulated AVP release in a dose-related fashion; the maximum effect occurred at a concentration of 1 mM [ratio of stimulated collection/basal collection: NMDA, 1.51 +/- 0.10, controls, 0.86 +/- 0.05 (mean +/- SEM); P < 0.001]. KA also showed a dose-related stimulatory effect in the dose range of 1 nM to 1 mM, with maximal AVP stimulation at 10 microM (KA, 1.91 +/- 0.28; controls, 0.90 +/- 0.03; P < 0.01). The effects of both NMDA and KA on AVP were completely reversed by the competitive antagonists D,L-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3 dione, respectively, at doses 10 times higher than those of the agonists. N-Methyl-D,L-aspartic acid stimulated AVP secretion only at a dose of 10 mM (P < 0.01), whereas quisqualate was ineffective at any concentration. The addition of 1 mM Mg2+ to the medium blocked the effect of NMDA, while attenuating AVP stimulation induced by KA. The stimulatory effect of KA on AVP was significantly reduced by D-L-2-amino-5-phosphonovaleric acid (P < 0.05), suggesting that KA may also act through NMDA receptors. Moreover, the presence of glycine in the incubation medium did not result in any effect of NMDA on CRH-41 secretion, nor did it appear to potentiate NMDA-induced AVP release.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Daily rhythms in the hormone content of the neurohypophysial system and release of oxytocin and vasopressin in the male rat: effect of constant light.

Patterns of neurohypophysial hormone secretion and changes in the hormone content of the hypothalamus and posterior pituitary lobe were monitored in the male rat for cycles of 24 h in association with changes in food and water intake and fluid excretion. Plasma oxytocin and vasopressin concentrations were seen to rise significantly over the hours of daylight, decreasing during the night. Parallel changes were seen in the immunoreactive material in the hypothalamus, whilst the content of the neurohypophysis was inversely related to plasma concentrations. The ratio of plasma oxytocin:vasopressin reached a significant peak at about 02.00 h which might be related to the feeding activity of the rats, food and water intake being largely confined to the night, as was fluid excretion. On exposure to constant light, despite initial disruption hormonal rhythms were still seen but showed a phase shift. The relationships between plasma and tissue levels were maintained. Patterns of food and water intake and urinary excretion were little affected by exposure to constant light, remaining largely confined to the former night phase. The hormonal rhythms appeared to be more closely related to the activity of the rats, which also showed a phase shift during constant light.

Animals↗