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R. J. Windle and M. L. Forsling

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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R J Windle and M L Forsling

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, J M Judah and R J Windle

Abstract

Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were detennined 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.

Journal of Endocrinology (1994) 141, 59–67

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R J Windle, J M Judah and M L Forsling

Abstract

The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12·7 ± 3·3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 ± 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 ± 5% (10 ng [mercapto-proprionic acid1,d-Tyr(Et)2, Thr4,Orn8]-oxytocin/min), 13 ± 5% (5 ng desGly9[d-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 ± 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 ± 5% associated with oxytocin infusion was significantly decreased to 4 ± 3% (5 ng desGly9[d-Trp2,d-Thr4,Orn8]-dC6oxytocin/min) and 1 ± 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10·1 ± 2·1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.

Journal of Endocrinology (1997) 152, 257–264

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R J Windle, J M Judah and M L Forsling

Abstract

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. Both fractional excretion of sodium and potassium excretion were also significantly elevated by this combined infusion, suggesting an additional tubular component to the response. Although no synergistic effect of neurohypophysial hormones on the antidiuresis was found in the conscious rat, they may act together to promote sodium excretion

Journal of Endocrinology (1995) 144, 441–448

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R. J. Windle, M. L. Forsling and J. W. Guzek

ABSTRACT

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.

Journal of Endocrinology (1992) 133, 283–290

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M L Forsling, Y Zhou and R J Windle

Abstract

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 μmol/min (n=32) to 18·3 ± 0·8 μmol/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.

Journal of Endocrinology (1996) 148, 457–464

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M. J. Brimble, R. J. Balment, C. P. Smith, R. J. Windle and M. L. Forsling

ABSTRACT

The contribution of oxytocin to the maintenance of renal Na+ excretion in the Brattleboro rat has been examined in animals infused with hypotonic saline. Brattleboro rats exhibited hypernatraemia and hyperosmolality associated with greatly increased plasma concentrations of oxytocin by comparison with Long–Evans control rats. Neurohypophysectomy to remove the secretion of the remaining posterior pituitary peptide, oxytocin, led to greatly diminished rates of Na+ excretion in the Brattleboro rat. Oxytocin replacement to achieve plasma levels equivalent to those in intact Brattleboro rats produced a substantial and sustained natriuresis in the neurohypophysectomized animal. Oxytocin secretion evoked in response to saline infusion would thus appear to be effective in promoting renal Na+ excretion in the absence of vasopressin in the Brattleboro rat.

Journal of Endocrinology (1991) 129, 49–54

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R. J. Windle, M. L. Forsling, C. P. Smith and R. J. Balment

ABSTRACT

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.

Journal of Endocrinology (1993) 137, 311–319