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M. L. Forsling
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L. A. Aziz
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Plasma vasopressin, arterial blood gas tensions, pH, arterial blood pressure, heart rate and respiration were monitored in conscious rats breathing room air or exposed to varying degrees of hypoxia. A similar series of observations was made in a group of anaesthetized rats and in rats treated with α- and β-adrenergic and dopaminergic blocking agents. The effect of two opioid antagonists on the vasopressin response was also noted. Hypoxia produced an increase in circulating vasopressin concentrations in both conscious and anaesthetized rats. In the conscious animals the increase reached statistical significance when the animals were exposed to 12% oxygen in nitrogen, which produced a fall in arterial PaO2 of 44·7 ± 5·0%. Guanethidine, phentolamine and propranolol all produced a significant fall in the basal concentrations of vasopressin, while guanethidine, phenoxybenzamine and propranolol blocked the increase seen on breathing 12% oxygen in nitrogen. Naloxone and levallorphan also reduced the vasopressin response to hypoxia. Thus it appears that aminergic pathways play a role in the maintenance of circulating concentrations of vasopressin and in the response to hypoxia. Endogenous opioids also appear to be involved in the hypoxic response.

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R J Windle
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M L Forsling
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Abstract

Oxytocin was administered to virgin female rats at doses of 25–200 pmol/min during 0·077 mol NaCl/l infusion at 150 μl/min on each day of the oestrous cycle. The resultant rates of urine flow, glomerular filtration (GFR) and electrolyte excretion were determined. Oxytocin caused significant increases in urine flow (P<0·001) and sodium excretion (P<0·001); both responses being dose-dependent (P<0·02 and P<0·01 respectively). Significant variations in the renal responsiveness to the hormone occurred over the 4 days of the oestrous cycle. On oestrus the lowest dose of 25 pmol oxytocin/min produced a significant increase in urine flow (from 139·5 ± 4·3 to 165·6 ± 7·1 μl/min, P<0·005) and a dose of 50 pmol/min produced a significant increase in sodium excretion (from 10·6 ± 0·1 to 14·5 ± 0·7 μmol/min, P<0·005). Significant increases in urine flow and sodium excretion were seen on pro-oestrus with hormone administration rates of 50 and 100 pmol/min respectively and on dioestrus day 2 with a rate of 100 pmol/min. On dioestrus day 1 no increase in urine flow or sodium excretion was seen over the dose range of oxytocin administration. A dose of 100 pmol oxytocin/min significantly increased GFR on pro-oestrus and dioestrus day 2, but not on the other 2 days of the cycle. The circulating hormone concentrations produced by oxytocin infusion were similar on each day of the cycle and so could not account for the differences seen. Therefore, these results suggest varying renal responsiveness to oxytocin during the reproductive cycle of the female rat.

Journal of Endocrinology (1997) 154, 347–353

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M. L. Forsling
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K. Peysner
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ABSTRACT

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.

J. Endocr. (1988) 117, 397–402

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K. Peysner
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M. L. Forsling
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ABSTRACT

Plasma vasopressin concentrations have previously been shown to vary during the oestrous cycle of the rat, being highest on the morning of pro-oestrus and lowest on dioestrus day 1. To determine the effect of gonadal steroids on vasopressin secretion and fluid balance, mature rats were ovariectomized and given oestrogen, progesterone or vehicle alone s.c. for periods of up to 16 days. Plasma vasopressin concentrations fell after ovariectomy and this was reflected in an increase in 24-h urine volume. The normal increase in plasma vasopressin concentrations seen over daylight hours was also suppressed. The change in vasopressin concentrations observed on steroid treatment depended upon both the dose and the duration. High doses of oestrogen were associated with a fall in plasma vasopressin, probably as a result of fluid retention. Thus, of an initial group of rats given silicone elastomer implants containing 50, 500 or 1000 μg oestradiol in oil, plasma vasopressin concentrations were reduced after 7 days treatment with 1000 μg oestradiol implants in association with reduced plasma sodium concentrations. Daily s.c. injections of 100 μg oestradiol benzoate/100 g body weight produced an immediate small increase in plasma vasopressin concentrations, but by 14 days the plasma concentrations of 0·7 ± 0·16 pmol/l (mean ± s.e.m.) had fallen significantly and were less than those in the vehicle-treated group (1·2± 0·26 pmol/l). However, after treatment for 14 days with implants containing only 50 μg oestradiol, plasma vasopressin concentations were higher compared with the group receiving vehicle alone, despite the fact that the plasma osmolality was lower in the latter group, suggesting a long term resetting of the osmoreceptors. Progesterone treatment with two implants containing 17·5 mg progesterone in oil was associated with an initial suppression of plasma vasopressin concentrations, but 16 days after the implant the plasma concentrations were higher than in the control group. Neither oestrogen nor progesterone restored the vasopressin concentrations to those seen in the intact animal. Oestrogen treatment resulted in a reduction in food and water intake, whereas progesterone treatment produced an initial increase in food and water intake, and a fall in plasma osmolality which could account for the reduced plasma vasopressin. This was followed by an increase in urine flow over days 6 to 15. Thus ovariectomy had a marked effect on circulating vasopressin concentrations, probably as a result of complex changes since administration of either oestrogen or progesterone in doses giving normal circulating concentrations had little effect.

Journal of Endocrinology (1990) 124, 277–284

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T. Wells
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M. L. Forsling
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ABSTRACT

A series of studies has been performed in the conscious rat to investigate the effect of the intracerebroventricular (i.c.v.) administration of the selective κ-opioid receptor agonist, U50 488H, on arginine vasopressin (AVP) secretion stimulated by i.c.v. administration of hypertonic NaCl. Similarly, the effect of the i.c.v. administration of morphine and the i.v. administration of naloxone on AVP secretion was investigated. The response of AVP to an i.c.v. injection of hypertonic NaCl was potentiated by naloxone at a dose of 0·4 mg/kg, but a higher dose (1·2 mg/kg) was required to increase the basal plasma concentration of AVP. Prior treatment with U50 488H or morphine attenuated the increase in plasma concentrations of AVP stimulated by i.c.v. injection of hypertonic NaCl from 13·92±4·44 to 1·22±0·34 and 1·78±0·74 pmol/l respectively (n = 7; P<0·05). Prior administration of U50 488H also attenuated the potentiating effect of naloxone on AVP secretion stimulated by i.c.v. injection of hypertonic NaCl. These results indicate that basal AVP secretion is under tonic inhibitory control by dynorphin, and that μ-and κ-opioid receptors mediate an inhibitory influence of endogenous opioids on osmoreceptor-mediated AVP secretion.

Journal of Endocrinology (1991) 129, 411–416

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R. J. Windle
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M. L. Forsling
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ABSTRACT

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.

Journal of Endocrinology (1993) 136, 305–311

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M. L. Forsling
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C. Matziari
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L. Aziz
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ABSTRACT

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 propanolol, phenyoxybenzamine and phentolamine produced a fall in resting vasopressin concentrations while propanolol 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.

J. Endocr. (1988) 116, 217–224

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M. L. Forsling
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H. Kelestimur
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R. Windle
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ABSTRACT

It has been shown that surgical ovariectomy of the rat results in a fall in plasma vasopressin concentrations suggesting that ovarian steroids may influence hormone release. To determine whether a similar fall is found on suppression of the oestrous cycle, vasopressin concentrations were monitored after treatment with the antioestrogen preparation tamoxifen or a long-acting analogue of LH-releasing hormone (LHRH) which suppresses ovarian function. Treatment with either agent was found to result in a fall in circulating vasopressin concentrations, with little effect on fluid balance. To determine whether the ovary could influence the vasopressin release in response to known stimuli, hormone concentrations were measured in ovariectomized animals during extracellular fluid hypertonicity produced by an i.p. injection of hypertonic saline and hypovolaemia produced by an i.p. injection of polyethylene glycol. It was found that after ovariectomy or treatment with tamoxifen, the response to hypertonicity was unaffected but that to hypovolaemia was attenuated. Treatment with LHRH affected the response to both hypovolaemia and hypertonicity.

Journal of Endocrinology (1991) 130, 387–393

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MARY L. FORSLING
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M. ÅKERLUND
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P. STRÖMBERG
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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.) μu./ml, while that on days 16–18 was 1·1±0·16 μu./ml. These values were significantly (P <0·02) different. Vasopressin release in women may thus depend on the hormonal changes during the menstrual cycle.

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Mary L. Forsling
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P. Strömberg
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M. Åkerlund
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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.

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