pituitrin and Weight-Gain

To investigate the effects of V1A receptor antagonist through inhibition of vasopressin-induced VEGF secretion in an experimental model.. Thirty rats were randomly divided into five groups. Four groups were given 10IU pregnant mare serum gonadotropin/day (sc) at 8:00-8:30am on days 22-25 of life. They were administered 30IU hCG at 8:00-8:30am on day 26 of life. On days 26 and 27 of life at 8:00am and 4:00pm, (ip) per animal, 50μg/kg/day GnRH antagonist in the GnRH antagonist group, 0.3mg relcovaptan in the high dose relcovaptan group, and 0.15mg relcovaptan in the low dose relcovaptan group were administered. The control group was given the same dosage of 0.9% saline solution (ip) on days 22-26 day of life. The main outcomes were weight gain, ovarian weights, peritoneal fluid VEGF values, corpus luteum count, and atretic follicle count.. Weight gain was highest in the OHSS group; it was almost twice as much in the OHSS group than it was in the control group. Ovarian weights were significantly lower in all treatment groups (p=0.03). There was no statistically significant difference in ovarian weights between the GnRH antagonist and relcovaptan groups (p=0.176). The evaluation of peritoneal fluid VEGF-A levels revealed statistically significant differences between levels in the treatment groups and in the OHSS group (p=0.005). Atretic follicle count in the OHSS group was significantly lower (p=0.048). In all treatment groups, CL counts were prominently lower than they were in the OHSS group (p=0.002).. Relcovaptan may be a novel strategy for decreasing risk of OHSS by inhibition of vasopressin-induced VEGF secretion through V1A receptor antagonist.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Ascitic Fluid; Chorionic Gonadotropin; Corpus Luteum; Disease Models, Animal; Female; Follicular Atresia; Gonadotropin-Releasing Hormone; Gonadotropins, Equine; Indoles; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pyrrolidines; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A; Vasopressins; Weight Gain

Nasal obstruction is a risk factor in sleep-disordered breathing with a negative impact on the quality of life in humans. We investigated hydration changes produced by short term reversible, bilateral, nasal obstruction in young developing rat pups. Physiological parameters of growth (weight gain and gastric content weight) and dehydration were analyzed during two periods; during nasal obstruction at post-natal day 8 (days 9, 11 and 13), plus 7 and 90 days after recovery of nasal breathing (day 15 and adulthood). Body weight gain in oral breathing rat pups was slower compared to controls. Gastric weight was decreased significantly only in oral breathing rat pups on days 9 and 11 while plasma osmolality and vasopressin levels increased (indicators of dehydration). There were no differences between controls and treated rat pups by day 15, or at adulthood. Short term nasal obstruction-induced forced oral breathing, decreased gastric content which had a negative impact on growth and blood glucose concentration in the short term for female rat pups. Plasma corticosterone levels increased during the dehydration but were normal in males by 90 days. This could be a model for blocked nose syndrome in the newborn. Possible long term consequences on development are discussed.

Topics: Adrenal Cortex Hormones; Analysis of Variance; Animals; Animals, Newborn; Behavior, Animal; Blood Glucose; Body Weight; Dehydration; Female; Male; Mouth Breathing; Organ Size; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Wistar; Sleep Apnea Syndromes; Stress, Psychological; Time Factors; Vasopressins; Weight Gain

Vasopressin and its receptors modulate several gut functions, but their role in intestinal inflammation is unknown. Our aims were to determine 1) the localization of V1b receptors in human and rodent colon, 2) the role of vasopressin and V1b receptors in experimental colitis using two approaches: V1b⁻(/)⁻ mice and a selective V1b receptor antagonist, SSR149415, and 3) the mechanisms involved. V1b receptors were localized in normal and inflamed colon from humans and rats. Experimental colitis was induced in rats and mice and some groups were treated before or after colitis induction with oral SSR149415 (3-30 mg/kg). Other groups of mice were submitted to dehydration to increase vasopressin plasma levels, prior to colitis induction. Body weight, damage scores, MPO, and TNF-α tissue levels were determined. Finally, colonic segments of wild-type (WT) and V1b⁻(/)⁻ mice were mounted in Ussing chambers and paracellular permeability in response to vasopressin was studied. V1b receptors were expressed in enterocytes and ganglia cells of the enteric nervous system of human and rat intestine. Expression levels were independent from inflammatory status. Colitis was less severe in rodents treated by either preventive or curative SSR149415 and in V1b⁻(/)⁻ mice. 2,4,6-Trinitrobenzene sulfonic acid induced a strong mortality in dehydrated animals that was reversed by preventive SSR149415 or mast cell stabilizer. Vasopressin significantly increased paracellular permeability in WT, but not in V1b⁻(/)⁻ mice. Preincubation of colon tissues with SSR149415 abolished the vasopressin effect. Similarly, vasopressin had no effect in colonic preparations from WT mice pretreated with mast cell stabilizers. Vasopressin, through V1b receptor interaction, has proinflammatory properties linked to mast cell activation and downstream alterations of the colonic epithelial barrier. These findings underline the potential interest of V1b receptor blockers in gut inflammatory diseases.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Colitis; Gene Expression; Gene Expression Regulation; Haptens; Humans; Indoles; Inflammatory Bowel Diseases; Mice; Phosphodiesterase Inhibitors; Pyrrolidines; Rats; Receptors, Vasopressin; Thioxanthenes; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha; Vasopressins; Water Deprivation; Weight Gain; Xanthones

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Aquaporin 6; Aquaporins; Electrophoresis, Polyacrylamide Gel; Female; Immunoblotting; Kidney; Kidney Function Tests; Liver Cirrhosis, Experimental; Membranes; Rats; Rats, Wistar; Receptors, Vasopressin; Renal Circulation; Sodium; Vasopressins; Water; Water-Electrolyte Balance; Weight Gain

Holstein bull calves were used to examine the effect of dry feed on water balance and fecal moisture content during the suckling period. In Experiment 1 (n = 20 calves), free access to concentrate and timothy hay decreased urine volume and increased apparent water retention, fecal water excretion, and fecal moisture content by 2 wk, although daily amounts of milk replacer also affected water balance when DMI from dry feed was low. In Experiment 2 (n = 20 calves), free access to concentrate and hay from wk 1 increased reabsorption of water from renal tubules during wk 2, resulting in reduced urine volume and increased plasma volume. In Experiment 3 (n = 10 calves), supplementation of 500 g/d of milk replacer plus free access to concentrate and hay from wk 1 increased plasma antidiuretic hormone by 2 wk compared with the concentration in calves receiving 200 g/d of milk replacer alone. Plasma antidiuretic hormone concentrations were highly correlated with plasma concentrations of acetate and ketone bodies but not with glucose and urea. In Experiment 4 (n = 16 calves), apparent water retention and fecal moisture content during wk 2 were increased by free access to concentrate from wk 1 but were not affected by rice straw as an inert bulk source.

Topics: Acetic Acid; Animal Feed; Animals; Animals, Suckling; Blood; Blood Urea Nitrogen; Body Water; Body Weight; Cattle; Feces; Ketone Bodies; Male; Milk; Osmolar Concentration; Urine; Vasopressins; Water; Water-Electrolyte Balance; Weight Gain

The mechanism causing peripheral oedema in hypoxaemic chronic obstructive pulmonary disease has not been established. Vasopressin, a powerful antidiuretic hormone involved in salt and water homeostasis, is released in response to acute hypoxia. However, the effect of prolonged hypoxaemia on hypothalamic and pituitary release of the magnocellular hypothalamic hormones, vasopressin and oxytocin, has not previously been studied.. Male Wistar rats were randomly allocated to either normobaric, hypoxic (10% O2) or control (21% O2) environmental chambers. An initial series of experiments examined plasma vasopressin concentration, osmolality, sodium concentration, packed cell volume (PCV), and weight gain at weekly intervals (n = 4-6) for six weeks. The maximum increase in plasma vasopressin concentration and PCV occurred after five weeks. In a second experiment vasopressin and oxytocin concentrations in the hypothalamus, pituitary gland, and plasma were measured in eight control and eight hypoxic rats after five weeks in the environmental chambers.. In rats exposed to environmental hypoxia PCV increased (p < 0.001) and weight gain decreased (p < 0.05) compared with controls. The plasma vasopressin concentration increased progressively from a baseline of 1.36 (0.2) pmol/l (n = 6) to a maximum of 4.38 (0.8) pmol/l (n = 6; p < 0.01) during the first five weeks of environmental hypoxia (difference 3.02 (95% CI 1.18 to 4.86)). Plasma osmolality and sodium concentration were unchanged in hypoxic rats compared with controls during the six week period. The hypothalamic vasopressin concentration was increased (p < 0.001) after five weeks of environmental hypoxia (91.6 (4.8) pmol/ hypothalamus) compared with controls (57.4 (5.1) pmol/hypothalamus), the difference being 34.2 pmol/hypothalamus (95% CI 21.6 to 46.5). The pituitary vasopressin concentration was unchanged. In hypoxic rats hypothalamic oxytocin (59.6 (3.2) pmol/hypothalamus) was greater (p < 0.01) than in controls (42 (3.8) pmol/hypothalamus), a difference of 17.6 pmol/ hypothalamus (95% CI 8.7 to 26.5). Similarly, the plasma oxytocin concentration was increased (p < 0.05) in hypoxic rats (6.78 (1.2) pmol/l) compared with controls (3.3 (0.8) pmol/l), a difference of 3.48 pmol/l (95% CI 0.89 to 6.07). The pituitary oxytocin concentration was unchanged in the two groups.. These results demonstrate an increase in hypothalamic production of vasopressin and oxytocin in rats during prolonged hypoxaemia. Increased plasma concentrations of neurohypophysial hormones would be expected to impair sodium and water homeostasis in patients with hypoxaemia. However, the absence of change in the plasma osmolality and sodium concentrations in this study and previous clinical investigations suggests that compensatory mechanisms modulate the actions of both vasopressin and oxytocin. A reduction in renal blood flow or decreased renal responsiveness to the neurohypophyseal hormones may be involved.

Topics: Animals; Hematocrit; Hypothalamus; Hypoxia; Male; Osmolar Concentration; Oxygen; Oxytocin; Pituitary Gland; Random Allocation; Rats; Rats, Wistar; Sodium; Vasopressins; Weight Gain

Elderly patients may exhibit changes in plasma hormone levels, as well as thirst disorders. Two groups of elderly hemodialysis patients were evaluated to determine if excessive interdialytic weight gain was related to differences in postdialysis plasma osmolality or postdialysis measurement of plasma renin activity, or plasma levels of angiotensin II (a dipsogenic hormone), aldosterone, and vasopressin. Patients mean age was 77.0 +/- 8.8 years and patients were divided into groups, I and II, with less than or greater than 2 kg interdialytic weight gain. Postdialysis plasma osmolality was similar in both groups of patients (309.3 +/- 2.3 vs. 309.6 +/- 2.4 mOsm/Kg, p = 0.8) and postdialysis AVP levels also were no different (2.7 +/- 0.6 vs. 2.1 +/- 0.2 pg/mL, p = 0.3). There was also no statistical difference between postdialysis angiotensin II and aldosterone levels in either group of patients. Plasma renin activity (PRA) was also not different in either group (2.3 +/- 1.1 vs. 0.43 +/- 0.1 ng/mL/hr, p = 0.1), but group I patients, with less than 2 kg weight gain, tended to exhibit higher PRA values perhaps reflecting proximity to their dry weight postdialysis. Since excessive fluid intake did not appear to relate to plasma osmolality and hormone levels studied, it might be suggested that excessive drinking could be due to excessive sodium intake associated with personal dietary habits or perhaps other as yet unmeasured factors.

Topics: Aged; Aged, 80 and over; Aldosterone; Angiotensin II; Humans; Kidney Failure, Chronic; Osmolar Concentration; Renal Dialysis; Renin; Vasopressins; Weight Gain

Ethanol ingestion affects the hypothalamo-neurohypophysial system resulting in increased diuresis, dehydration and hyperosmolality. We studied the supraoptic nucleus, of the hypothalamus, in ethanol-treated rats, to determine if ethanol alone and/or the associated disturbances of water metabolism lead to structural alterations in a nucleus known to play a central role in fluid homeostasis. Groups of male and female rats were ethanol-treated until 12 and 18 months of age and compared with age-matched pair-fed controls. Twelve and 18-month-old control groups and 12-month-old water control groups (rats submitted to chronic dehydration) were also included in this study in an attempt to differentiate between the effects of undernutrition and dehydration/hyperosmolality, and the specific neurotoxic effects of ethanol. We estimated the volume of the supraoptic nucleus and the numerical density of its neurons and calculated the total number of supraoptic neurons. The volume of both supraoptic neurons and neuropil were also estimated. In immunostained material the ratio of vasopressin to oxytocin neurons and the cross-sectional areas of the two neuronal types were evaluated. There was marked neuronal loss in alcohol-treated rats, but the volume of the supraoptic nucleus was increased. The increase in the volume of the supraoptic nucleus correlated with and was due to increases in the volume was particularly marked for vasopressin neurons. No significant differences were found between controls and pair-fed controls in any of the parameters investigated. In water control rats, the volume of the supraoptic nucleus and of the supraoptic neurons and neuropil was also greater than in pair-fed controls. However, the variations found were not as marked as in ethanol-treated rats and there was no cell loss. These findings reveal, for the first time, that chronic ethanol consumption affects the morphology of supraoptic neurons and neuropil and, consequently, the structure of the entire supraoptic nucleus. Moreover, this study supports the view that ethanol has direct neurotoxic effects on supraoptic neurons because the alterations that occur are not mimicked in animals in which water metabolism alone is disturbed.

Topics: Animals; Brain; Dehydration; Ethanol; Female; Immunohistochemistry; Male; Neurons; Organ Size; Oxytocin; Rats; Rats, Wistar; Sex Characteristics; Supraoptic Nucleus; Vasopressins; Water-Electrolyte Balance; Weight Gain