Vasopressin

Antidiuretic hormone liberated the vertebrates from their aqueous environment, and permitted them to establish themselves on dry land. The combination of sensitive volume and osmoreceptors, a pituitary secretory apparatus which can vary its output from virtually zero to high levels in a short space of time, and receptor cells functioning in the countercurrent system of the renal medulla, has resulted in a water conservation system of great efficiency. The hormone rapidly alters the luminal membrane of receptor cells in the collecting tubule and collecting duct, increasing the permeability of these structures to water.1 The permeability of the collecting duct to urea and sodium is also increased.This review will be centered on the sequence of events that follows the attachment of vasopressin to its receptors in the distal nephron. This has become an area of intense activity since the discovery by Sutherland and his colleagues of the central role of cyclic AMP in the action of hormones [2]. The review will cover in brief much of the ground covered by the extensive review of Handler and OrlofT [3], emphasizing recent additions to the literature. It is regrettable that the important advances in our understanding of the synthesis and release of antidiuretic hormone cannot be included; the reader is referred to recent symposia and reviews in this area [4–6], as well as in the comparative physiology of water regulation [7] and the countercurrent system [8]

An Examination of the Hypothalamo-neurohypophysial System of the Rat: Restoration of the Vasopressinergic System

The hypothalamo-neurohypophysial model has been studied for many years. Of note, when the axons of the magnocellular, peptidergic neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are transected or crushed, varying degrees of polydipsia and polyuria ensue as the result of measurable losses of vasopressin (AVP) within the organism\u27s circulation. Following insult, these hypothalamic cells show a remarkable capacity to reorganize themselves within the proximal areas of the infundibular stalk and median eminence and form what has come to be known as a new \u27mini neural lobe\u27 . While the surviving neurons sprout new projections toward the level of the external zone, vascular hypertrophy is marked throughout the new neurohypophysis and new neurohemal contacts have been identified (at the ultrastructural level) associated with these vessels. In parallel with this vascular hypertrophy is a measurable re-release of vasopressin into the circulation. This new \u27mini neural lobe\u27 now has the morphological and physiological appearance of an intact neural lobe and is capable of releasing AVP in response to changes in water balance. While the ability of these axons to reorganize is more characteristic of the peripheral nervous system (PNS), this model system provides an unique opportunity to study axonal regeneration of the central nervous system (CNS). Not only the mechanisms underlying the restoration of AVP function following axotomy but the extent to which various magnocellular neuron populations are involved in the regenerative process may also be analyzed. Before attempting to identify putative markers associated with this regenerative process, it was necessary to carefully characterize the system following axonal injury. Using Sprague Dawley rats, we repeated previous physiological studies which had examined the intake of water and output of urine following hypophysectomy. In addition, we also correlated the restoration of water balance with the return of AVP release, as measured by radioimmunoassay. These data defined a temporal framework in which magnocellular AVP regeneration occurs. As a result of repeating these physiological studies, we noted several inconsistencies between other previously published work. First, the time course of AVP recovery did not agree with other published results, nor did the first appearance of AVP immunoreactivity . We did not observe a complete recovery of water balance as previously reported and the degree of magnocellular death was inconsistent with other reports. In light of these many conflicting observations between several historical reports and our own results, we did a basic physiological re-characterization of the hypothalamo-neurohypohysial system following hypophysectomy. By means of immunohistochemistry, we also demonstrated the re-appearance of AVP within the new the \u27mini neural lobe \u27 concomitant with the increased appearance of synapsin I, a marker associated with the presence of mature and presumably functioning synapses to be no sooner than 28 days following surgical removal of the hypophysis. Immunocytochemistry was also used in conjunction with retrograde fluorescent labeling to extend the previous studies and include a 2-D analysis of cell survival throughout the PVN and SON following hypophysectomy or neurohypophysectomy. As reported previously, magnocellular neuronal loss is greater within the SON, particularly the hypophysectomized subject, and less so within the PVN; again with the greater loss in the PVN of the hypophysectomized animal. Based upon our observations and other recent reports, we suggest the possibility that some cells of the hypothalamo-neurohypophysial system or some other extrahypothalamic cell population may be capable of expressing vasopressin in response to neurohypophysectomy. We provide initial evidence that glial cells of the third ventricle may indeed be involved. Finally, one of the ultimate goals of using this as a model system of CNS regeneration is to understand the underlying mechanisms and components essential to central nervous tissue regeneration. Toward that end I have been involved with the initial studies to optimize an adenovirus delivery system which will be capable of incorporating various putative neurotransmitter and/or peptide anti-sense messages, being injected into the neurohypophysis and transported back into the cells of the hypothalamo-neurohypophysial system. Once these antisense sequences are expressed by the cells following axotomy, the sequence of expression of various proteins in response to injury may be elucidated

Determinants of Plasma Copeptin in Newborns at Birth and During Postnatal Adaptation

Background. Arginine vasopressin (AVP) is a key hormone in regulating blood pressure and body water balance, but despite modern procedures remains difficult to measure. Copeptin, the carboxyl-terminus portion of the AVP precursor, is much more stable and presents a reliable alternative to measuring the secretion of AVP. Copeptin has been studied to great extent in adults and is emerging as a useful diagnostic and prognostic biomarker for a variety of diseases. As of now there has been no research on copeptin in pediatric medicine. The aim of this study was to assess the normal basal values of plasma copeptin in infants in the first days of life and to investigate influencing factors at birth and during early postnatal adaptation

The distribution and functions of melanin-concentrating hormone in lower vertebrates

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN009077 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Atrial natriuretic peptide in liver disease with sodium retention

Plasma concentration of atrial natriuretic peptide (ANP), measured by radioimmunoassay, was increased in patients with cirrhosis and ascites as compared to age matched healthy controls under basal conditions and throughout 24 hours of observation. Nocturnal natriuresis in patients, between midnight and 0800 hours, coincided with a marked reduction in the activity of the renin-aldosterone system. During this period there was significant correlation between urine sodium and plasma AJP concentration, suggesting that a). ANP may have a role in nocturnal natriuresis in cirrhosis and b). a reduction of renin-aldosterone in recumbency, may allow the natriuretic effect of ANP to become manifest. In the course of therapeutic paracentesis for tense ascites, plasma ANP tended to rise initially, in parallel with an increase in cardiac output and a drop in right atrial pressure, findings consistent with atrial decompression. Investigation by 2D-echo-cardiography, confirmed the presence of compression of the right atrium in patients with tense ascites. Plasma concentration of AHP in patients with paracetamol-induced fulminant hepatic failure was similar to that in healthy controls, but was increased in the presence of severe renal failure. Alterations in fluid balance, induced by haemodialysis and infusion of Human Albumin solution, resulted in appropriate changes of plasma AJTP. These findings indicate that a), there is no deficiency of AITP in fulminant hepatic failure and b). known mechanisms of ANP release are not impaired. In rats with carbon tetrachloride-induced cirrhosis, plasma ANP concentration was higher than in control animals. In cirrhotic rats with impaired sodium excretion in-vivo, there was diminished natriuretic response to infusion of synthetic AJP at physiological and pathophysiological concentrations, suggesting that in this animal model of cirrhosis, renal resistance to the natriuretic action of ANP may contribute to sodium retention

Natriuretic peptides and their receptors in the brain of the amphibian, Bufo marinus

The natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are members of a family of hormones that play an important role in mammalian fluid and electrolyte balance. In the periphery, natriuretic peptides reduce blood volume and subsequently blood pressure by increasing renal natriuresis and diuresis and relaxation of vascular smooth muscle. The actions of natriuretic peptides are mediated via two membrane-linked guanylate cyclase receptors (NPR-GC); natriuretic peptide receptor-A (NPR-A) which has a high affinity for ANP and BNP; and natriuretic peptide receptor-B (NPR-B)which has the greatest affinity for CNP. A third receptor not linked to guanylate cyclase, natriuretic peptide receptor-C (NPR-C) also exists, which binds to ANP, BNP and CNP with a relatively equal affinity, and is involved with clearance of the peptides from the circulation and tissues. The natriuretic peptides are present in the brain and are particularly predominant in cardiovascular and fluid and electrolyte regulating areas such as the anteroventral third ventricle (AV3V) region. This distribution has led to the suggestion natriuretic peptides play a neuromodulatory role in the central control of fluid homeostasis. Natriuretic peptides in the brain have been observed to inhibit the release of other fluid and electrolyte regulating hormones such as arginine vasopressin (AVP) and angiotensin II (AII). Natriuretic peptides have also been identified in the non-mammalian vertebrates although information regarding the distribution of the peptides and their receptors in the non-mammalian brain is limited. In amphibians, immunohistochemical studies have shown that natriuretic peptides are highly concentrated in the preoptic region of the brain, an area believed to be analogous to the A\T3\ region in mammals, which suggests that natriuretic peptides may also be involved in central fluid and electrolyte regulation in amphibians. To date, CNP is the only natriuretic peptide that has been isolated and cloned from the lower vertebrate brain, although studies on the distribution of CNP binding sites in the brain have only been performed in one fish species. Studies on the distribution of ANP binding sites in the lower vertebrate brain are similarly limited and have only been performed in one fish and two amphibian species. Moreover, the nature and distribution of the natriuretic peptide receptors has not been characterised. The current study therefore, used several approaches to investigate the distribution of natriuretic peptides and their receptors in the brain of the amphibian Bufo marinus. The topographical relationship of natriuretic peptides and the fluid and electrolyte regulating hormone arginine vasotocin was also investigated, in order to gain a greater understanding of the role of the natriuretic peptide system in the lower vertebrate brain. Immunohistochemical studies showed natriuretic peptides were distributed throughout the brain and were highly concentrated in the preoptic region and interpeduncular nucleus. No natriuretic peptide-like immunoreactivity (NP-IR) was observed in the pituitary gland. Arginine vasotocin-like immunoreactivity (AvT-IR) was confined to distinct regions, particularly in the preoptic/hypothalamic region and pituitary gland. Double labelling studies of NP-JR and AvT-IR showed the peptides are not colocalised in the same neural pathways. The distribution of natriuretic peptide binding sites using the ligands 125I-rat ANP (125I-rANP) and 125I-porcine CNP (125I-pCNP) showed different distributions in the brain of B. marinus. The specificity of binding was determined by displacement with unlabelled rat ANP, porcine CNP and C-ANF, an NPR-C specific ligand. 125I-rANP binding sites were broadly distributed throughout the brain with the highest concentration in pituitary gland, habenular, medial pallium and olfactory region. Minimal 125I-rANP binding was observed in the preoptic region. Residual 125I-rANP binding in the presence of C-ANF was observed in the olfactory region, habenular and pituitary gland indicating the presence of both NPR-GC and NPR-C in these regions. 125I-pCNP binding was limited to the olfactory region, pallium and posterior pituitary gland. All 125I-pCNP binding was displaced by C-ANF which suggests that CNP in the brain of B. marinus binds only to NPR-C. Affinity cross-linking and SDS-PAGB demonstrated two binding sites at 136 kDa and 65 kDa under reducing conditions. Guanylate cyclase assays showed 0.1 µM ANP increased cGMP levels 50% above basal whilst a 10-fold higher concentration of CNP was required to produce the same result. Molecular cloning studies revealed a 669 base pair fragment showing 91% homology with human and rat NPR-A and 89% homology with human, rat and eel NPR-B. A 432 base pair fragment showing 67% homology to the mammalian NPR-C and 58% homology with eel NPR-D was also obtained. The results show natriuretic peptides and their receptors are distributed throughout the brain of B. marinus which indicates that natriuretic peptides may participate in a range of regulatory functions throughout the brain. The potential for natriuretic peptides to regulate the release of the fluid and electrolyte regulating hormone AVT also exists due to the high number of natriuretic peptide binding sites in the posterior pituitary gland. At least two populations of natriuretic peptide receptors are present in the brain of B. marinus, one linked to guanylate cyclase and one resembling the mammalian clearance receptor. Furthermore, autoradiography and guanylate cyclase studies suggest ANP may be the major ligand in the brain of B. marinus, even though CNP is the only natriuretic peptide that has been isolated from the lower vertebrate brain to date