Lack Of Vasopressin Research Articles

Diabetes insipidus: Overview

Diabetes insipidus is mainly characterized by polyuria, urinary volume over 3 L/day or 40mL/kg/day in adults, leading to subsequent polydipsia; these features are also present in most cases of diabetes mellitus. But today we can use natural treatment to remedy our problems concerning diabetes. This review is about diabetes insipidus which is entirely different from diabetes mellitus. We have read much about diabetes mellitus but now we must know about the diabetes insipidus. Diabetes insipidus is a uncommon condition, in which the kidneys are unable to conserve water. The amount of water which is conserved by the kidney is controlled by anti diuretic hormone (ADH) also called as vasopressin. In this disease there is lack of vasopressin in the body. In this overview there is a full disease profile of diabetes insipidus, so we came to know about the causes, sign & symptoms, treatment and medication for this diease.

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Lack of vasopressin does not prevent the behavioural and endocrine changes induced by chronic unpredictable stress

Vasopressin (VP) plays an important role in hypothalamo–pituitary–adrenal (HPA) axis regulation and in stress-related disorders. Our previous studies confirmed the role of VP in acute situations, where VP-deficient Brattleboro rats had less depression-like behaviour compared to animals that express VP. In this study, we test the hypothesis that VP-deficient rats are more resistant to the development of chronic HPA axis hyperactivity and depression-like symptoms after chronic unpredictable stress (CUS). Male VP-deficient Brattleboro rats were compared to their heterozygous littermates (controls). CUS consisted of different mild stimuli for 5 weeks. Elevated plus maze and forced swim test were used for behavioural characterization, while organs and blood for HPA axis parameters were collected at the end of the experiment. In controls, CUS resulted in the development of chronic stress state characterized by typical somatic (body weight reduction, thymus involution) and endocrine changes (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in anterior lobe of the pituitary). Floating time in the forced swim test was enhanced together with reduced open arm entries on elevated plus maze and a reduction in daily food intake. Unexpectedly, the lack of VP did not alter the effect of CUS on the somatic and behavioural measures, but only prevented CUS-induced corticosterone changes. In conclusion, lifelong VP-deficiency has a positive effect on corticosterone elevation following CUS but does not affect the behavioural consequences of CUS. It is likely that the interplay of several related factors, rather than an alteration in a single neuropeptide, modulates behaviour and disease pathogenesis.

Postnatal development in vasopressin deficient Brattleboro rats with special attention to the hypothalamo-pituitary–adrenal axis function: the role of maternal genotype

Anomalies in hormonal and neurotransmitter status during perinatal period can lead to lifespan alterations in the central nervous system. Vasopressin is present early in the brain and has various mitogenic, metabolic and physiological actions, e.g. in water homeostasis or in the regulation of the hypothalamo-pituitary–adrenal (HPA) axis. Therefore we examine the possible role of vasopressin in perinatal development with special attention to the influence of maternal genotype and to the HPA axis regulation. We compared homozygous vasopressin deficient (di/di) Brattleboro rats to their heterozygous (di/+) littermates both from di/+ and di/di mother. Higher locomotion due to reduced adaptation was present at preweaning. During the first 10 days of life the di/di pups from di/di mother were the smallest, while in the later perinatal period the genotype of the pups became the more important determinant of the somatic development, namely the di/di pups from both mothers had reduced weight gain. Generally the lack of vasopressin in the pups fastened the somatic development (pinna detachment, eye and ear opening, incisor eruption) however the neurobehavioral development (palmar grasp reflex, righting reflex, negative geotaxis, etc.) was not influenced profoundly by either the mother's or the pup's genotype. The lack of vasopressin in pups abolished the 24h maternal separation induced adrenocorticotrop hormone (ACTH) elevation while the accompanying corticosterone rises were even higher. The vasopressin deficiency of the mother reduced the resting ACTH and all corticosterone levels in all pups. So we can conclude that the lack of vasopressin speeds up the development, probably there is a greater drive for self-sufficiency in these animals. The mother's vasopressin deficiency reduced the HPA axis reactivity of the pups. The role of vasopressin in the HPA axis regulation is important during the perinatal period independently from the mother's genotype. The large discrepancy between ACTH and corticosterone regulation requires further studies.

Paraventricular nucleus influence on renal sympathetic activity in vasopressin gene‐deleted rats

In Wistar rats, an increase in renal sympathetic activity is induced by activation of presympathetic neurones in the paraventricular nucleus (PVN) and reflexly by a mild venous haemorrhage. Both stimuli are dependent on the release of vasopressin and glutamate at spinal synapses. The significance of the supraspinal pathway and the co-operative interaction of vasopressin with an excitatory amino acid is unclear. The present study examines this in Brattleboro rats, which have a natural vasopressin gene deletion. The responses were compared with Long-Evans rats, from which Brattleboro rats are derived. All rats were anaesthetized with a mixture of urethane (650 mg kg(-1) i.v.) and chloralose (50 mg kg(-1) i.v.). Recordings were made of blood pressure, heart rate and renal sympathetic nerve activity (RSNA). Microinjection of d,l-homocysteic acid (DLH, 0.2 m, 100 nl) at sites restricted to the PVN elicited significant increases in RSNA (P < 0.001) in both strains of rats. These changes were significantly reduced (P < 0.01) in Long-Evans rats by intrathecal application to the spinal cord of either a V(1a) antagonist or a glutamate antagonist (kynurenic acid), whereas in Brattleboro rats the changes were significantly reduced (P < 0.05) only by kynurenic acid. Removal of 1 ml of venous blood in Long-Evans rats increased RSNA by 28 +/- 4% (P < 0.01), which was significantly reduced (P < 0.05) by prior intrathecal application of either the V(1a) antagonist or by kynurenic acid. The same test in Brattleboro rats caused a significantly greater (P < 0.05) increase (63 +/- 14.7%) in RSNA which, in contrast to Long-Evans rats, was unchanged by intrathecal application of the V(1a) antagonist, being significantly reduced (P < 0.01) only by intrathecal kynurenic acid. Thus, in Brattleboro rats, the lack of vasopressin in the brain sympathetic pathways appears to be compensated, acutely, by glutamate-releasing pathways. This might indicate that, in normal rats, vasopressin is more important in maintaining longer term adjustments to stressors.

Collecting duct (Na+/K+)-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes.

In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.

Water deprivation induces regional expression of c- fos protein in the brain of inbred polydipsic mice

We studied the effects of water deprivation on the expression of c- fos protein (Fos) in the brain of inbred polydipsic mice, STR/N strain, that show extreme polydipsia without a lack of vasopressin in the body. Non-polydipsic mice, ICR strain, were used as controls. All male animals were deprived of water for 24 and 48 h. Fos-like immunoreactivity (Fos-LI) in the brain was studied by immunohistochemical techniques. In both groups of mice water deprivation induced a remarkable increase in Fos-LI in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, the median preoptic nucleus (MnPO), the organum vasculosum laminae terminalis (OVLT) and the subfornical organ (SFO). A far more increase, however, was seen in the MnPO, the SFO and the area postrema (AP) of the polydipsic mice compared to those of the non-polydipsic control mice. In the nucleus of the tractus solitarius (NTS) and in the anteroventral part of the PVN (avPVN), water deprivation caused a clear increase in Fos-LI in the polydipsic mice, while in the non-polydipsic mice the same treatment induced no Fos-LI in the NTS and no change in the avPVN. These results indicate that neurons in the circumventricular organs and the NTS are strongly activated by water deprivation in the polydipsic mice, suggesting that these brain structures play an important role in the polydipsia.

Effect of median eminence lesion on the hypertensive response due to acute aortic coarctation

The present study was designed to investigate the effect of a lack of vasopressin resulting from electrolytic lesion of the median eminence of the hypothalamus on the acute 45-min aortic coarctation hypertension elicited in conscious rats by means of a pneumatic cuff placed around the aorta above the renal arteries. Forty-eight hours after lesion, aortic constriction elicited a prompt (5-min) rise in mean carotid pressure from 115 +/- 2 to 149 +/- 2 mmHg, followed by a gradual decline to 129 +/- 2 mmHg. In contrast, sham-lesioned rats exhibited a prompt hypertensive response from 118 +/- 2 to 157 +/- 2 mmHg that leveled off throughout the experiment. Lesioned rats treated with saralasin presented a blunted hypertensive response (within 125 +/- 2 to 130 +/- 2 mmHg), whereas sham-lesioned rats showed only a delay in the onset of hypertension. The hypertensive response of lesioned rats was unaffected by the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP, whereas sham-lesioned rats submitted to this treatment presented a prompt rise in pressure followed by a gradual decline at the end of the experiment. Lesioned and sham-lesioned rats treated with saralasin plus vasopressin antagonist showed a blunted hypertensive response throughout the experiment. These data demonstrate that the integrity of the median eminence plays a pivotal role in the maintenance (30-45 min) of acute aortic coarctation hypertension, presumably involving the release of vasopressin from the neurohypophysis, whereas angiotensin II mainly accounts for the prompt (5-15 min) rise in pressure.

Brain adrenocorticoid receptor binding capacity in the diabetes insipidus brattleboro rat is dependent on maternal genotype.

We examined whether a different maternal genotype might differentially affect the brain adrenocorticoid receptor in homozygous diabetes insipidus Brattleboro rats. Two distinct homozygous diabetic offsprings were studied in comparison with Long Evans (LE) rats: one born of a homozygous mother (DI/HOM MOTHER), and the other born of a heterozygous mother (DI/HET MOTHER). The number of type I adrenocorticoid receptors of DI/HET MOTHER rats was significantly lower than that of LE rats in the hippocampus and hypothalamus, while in the amygdala both type I and type II receptors decreased. Surprisingly, the binding capacity of DI/HOM MOTHER rats, notwithstanding the absence of vasopressin (VP), as in the DI/HET MOTHER, did not differ from that of LE. Superimposable results were obtained in all the brain regions examined. No differences in binding affinity values (Kd) were detected. It was hypothesized that an 'unknown factor' linked to the genotype of the homozygous diabetic mother might counterbalance the receptor deficit otherwise induced by the lack of VP. The existence of two subpopulations of diabetic Brattleboro rats, as used in this study, should prompt to reexamine the origins of some behavioral and endocrine discrepancies appearing in studies on the homozygous diabetes insipidus Brattleboro strain.

Natural killer cell activity in vasopressin-deficient rats (brattleboro strain)

Several lines of evidence suggest that the neuropeptide vasopressin is involved in the regulation of the immune system. We explored this possibility by comparing the cytotoxic activity of natural killer (NK) cells in Brattleboro (DI) rats were derived. Additionally, we compared insipidus and lack vasopressin, and Long-Evans (LE) rats, the strain from which are homozygous for diabetes the effects of swim stress, morphine administration and vasopressin replacement on NK cell activity in these two strains. In DI rats, NK cell activity, determined by a standard 4-h chromium-release assay, was significantly higher than in LE rats. Both swin stress and morphine administration suppressed NK activity in DI and LE rats. There was no difference in the level of suppression between the two strains. Vasopressin replacement normalized water intake in DI rats, but had no significant effect on NK cell activity. DI rats exhibited lower plasma corticosterone levels, which were not elevated by vasopressin replacement. The results suggest that the lack of vasopressin in DI rats elevates baseline NK cell activity, probably via mechanisms that are secondary to the vasopressin deficiency (e.g. lower corticosterone levels). Neither vasopressin nor other hormones affected by vasopressin deficiency seem to be involved in the acute modulating effects of stress and morphine on NK cells.

Central vasopressin system mediation of acute pressor effect of gamma-MSH.

Intravenous (iv) administration of gamma-melanocyte-stimulating hormone (gamma-MSH) produces central sympathetically mediated pressor and cardioaccelerator effects and increases the activity of hypothalamic vasopressinergic neurons. The autonomic actions are similar to infusion of vasopressin (Vp) into the hindbrain of 4th ventricle (Ven). To ascertain whether activation of the central Vp system is the proximate cause of the pressor effects of gamma-MSH, we investigated the effects of gamma-MSH in rats pre- and postblockade of central nervous system Vp receptors and in rats with a hereditary lack of vasopressin (Brattleboro strain). Central Vp receptor blockade significantly reduced (80%) the pressor effects of iv gamma-MSH. As a control, iv administration of the antagonist, while effective in blocking the pressor effect of iv Vp, had no effect on the gamma-MSH pressor response. When compared with their genetic controls (Long-Evans strain), Brattleboro rats also had greater than 80% reduction in their pressor response to iv gamma-MSH. The results indicate that circulating gamma-MSH activates the central Vp system to produce its sympathoexcitatory pressor effects.

Delayed ontogenesis of histamine in the hypothalamus of the homozygous Brattleboro rat.

The ontogenetic development of histamine was studied in the diabetes insipidus rat to clarify the possible interference between the lack of vasopressin and the development of histaminergic systems in the hypothalamus. Rat pups were decapitated at different ages between the 2nd and 38th postnatal days. In addition to homozygous Brattleboro (diabetes insipidus) rats, Long Evans controls and heterozygous animals were studied. In all three genotypes hypothalamic histamine was almost equal during the first 6 postnatal days. In homozygous Brattleboro rats the period of most rapid increase occurred between days 14 to 26, which was significantly later than in Long Evans rats. In the remainder of the brain no such difference was seen. On the contrary, histamine values were highest in the youngest animals. It remains to be elucidated whether the delayed ontogenesis is causally related to vasopressin deficiency and what is the underlying mechanism.

Involvement of vasopressin in brain edema formation: further evidence obtained from the Brattleboro diabetes insipidus rat with experimental subarachnoid hemorrhage.

Brain water accumulation (1.2%) with an accompanying increase in the sodium content was observed in Wistar rats as early as 1 hour after experimental subarachnoid hemorrhage (SAH). After 6 and 24 hours, the water content was 1.3 and 1.4%, respectively, higher than that of control animals. In contrast, in Brattleboro diabetes insipidus rats the content of brain water and electrolytes had not changed significantly 1 hour after the administration of blood into the subarachnoid space. Increased brain water and sodium and a normal potassium content, indicative of a vasogenic type of brain edema, were seen at 6 hours after SAH. In these animals, known to be devoid of vasopressin, the increase in brain water 24 hours after SAH was 2.6%, compared with 1.4% for Wistar rats with SAH. It is suggested that the lack of vasopressin could alter the course of brain edema formation after experimental SAH in Brattleboro diabetes insipidus rats. It is hypothesized that vasopressin, by regulating the water permeability of the brain capillaries, the choroid plexus, and the cerebrospinal fluid absorption structures, plays an important role in controlling the brain fluid and electrolyte balance during the course of SAH.

Self-starvation and activity stress in Brattleboro rats

In order to examine the susceptibility of Brattleboro rats to self-starvation and activity stress, as evidenced by ulcer formation, four conditions were studied: (1) ad-lib access to food and water in an individual home cage, (2) ad-lib access to food and water in an activity-wheel cage, (3) ad-lib access to water and 1-h access to food in an individual home cage, and (4) ad-lib access to water and 1-h access to food each day in an activity-wheel cage. In the first two conditions, neither Brattleboro nor control animals developed ulcers. In the third condition, some rats in each group developed pits in the glandular portion of the stomach. Significant differences appeared in the fourth condition. Brattleboro rats developed more stomach pathology in both the nonglandular and glandular portions of the stomach than controls. The results were not due to variations in running behavior. The data indicate that the lack of vasopressin or physiological results of this deficit render Brattleboro rats more sensitive to self-starvation and activity stress than control animals.

Circadian rhythms in vasopressin deficient rats

Circadian rhythms in wheel running and drinking behavior were investigated using heterozygous an homozygous (diabetes insipidus) female Brattleboro rats Despite the lack of vasopressin in the suprachiasmatic nuclei of the diabetic rats, they showed coherent rhythms, both in cyclic light and in constant light. However, the periods of the free-running rhythms were longer for the diabetic rats, they were less active, and, of course, were severely polydipsic. Replacement treatment with systemic infusions of vasopressin reversed the polydipsia but did not affect the other measures.