Molecular Physiology of Water Balance

Abstract

T he hypothalamic-neurohypophyseal-renal axis normally maintains water balance during variations in water intake and nonrenal losses of water. Failure of this mechanism is common in hospitalized patients, and it results in a variety of water-balance disorders. In this article, we begin by reviewing the classic, integrative principles of water balance in mammals and then use this classic model as a framework to discuss the genes and gene products (proteins) involved in water balance. In so doing, our goal is to provide clinicians with a mechanistic basis for decisions regarding the diagnosis and treatment of waterbalance disorders.The regulation of water balance is governed by a high-gain feedback mechanism involving the hypothalamus, the neurohypophysis, and the kidneys (Fig. 1). Osmoreceptors in the hypothalamus, which originally were described by Verney, 1 sense plasma osmolality. The molecular mechanism of "osmosensing" has recently been described by Danziger and Zeidel. 2 It is, in part, dependent on activation of nonselective calcium-permeable cation channels in osmosensing neurons that can serve as stretch receptors.When plasma osmolality increases to levels above a physiologic threshold (290 to 295 mOsm per kilogram of water in most persons), there is increased secretion of the peptide hormone vasopressin from vasopressinergic nerve endings in the neurohypophysis. High osmolality also triggers thirst. Vasopressin binds to receptors in the kidney that decrease excretion of water (Fig. 2), and a greater fraction of filtered water is returned to the blood. The rate of water excretion can vary over a broad range in response to changes in plasma vasopressin levels without substantial changes in net solute excretion (osmolar clearance). This independent control of water and solute excretion is the result of specialized urinary concentrating and diluting mechanisms; these mechanisms are reviewed elsewhere. 3 Increased renal reabsorption of water in response to vasopressin lowers plasma osmolality, thereby reducing the stimulus for vasopressin secretion and thirst and completing the feedback loop (Fig. 1). Table 1 provides a list of the major proteins that are responsible for components of the integrative model shown in Figure 1. These proteins are the focus of this review. A rginine Va sopr essinThe gene coding for arginine vasopressin (AVP) is expressed in neurons of the supraoptic and paraventricular nuclei of the hypothalamus. Arginine vasopressin is a typical neuropeptide, since its gene codes for a prohormone that must undergo specific proteolytic processing to produce the active hormone. Thus, AVP codes for three peptides -the 9-amino acid peptide arginine vasopressin, a car-

Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action of TUG Protein in Muscle

“…1D shows that AQP2 protein was less abundant in kidneys of water-deprived mTUG UBX-Cter mice, when compared with wild-type controls. Renal AQP2 is present exclusively in parts of the nephron where vasopressin regulates the osmotic transport of water to concentrate urine (32). Although other cells contribute material to whole kidney lysates, gross and histologic studies revealed no differences between kidneys of transgenic and wildtype mice (6).…”

“…Vasopressin regulates water permeability in the renal collecting system by both minute-to-minute effects on AQP2 targeting and hour-to-daylong effects on AQP2 abundance (30,32). We considered that the longer-term effects on AQP2 abundance would be most relevant in mTUG UBX-Cter transgenic mice, which are predicted to have chronically accelerated inactivation of circulating vasopressin.…”

Novel Therapeutic Strategies Targeting Molecular Pathways of Cystogenesis in Autosomal Polycystic Kidney Disease

“…As a result, this normally water-tight membrane becomes water-permeable. Driven by the osmotic gradient of sodium, water is then transcellularly reabsorbed, entering the cells through aquaporin-2 in the apical membrane and leaving the cells for the interstitium through aquaporin-3 and aquaporin-4, which reside in the basolateral membrane (31). In patients with ADPKD, there is a pathologically hyperactive AVP/V2 receptor system.…”

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

“…57 There are four types of AVP receptors, namely, V1a, V1b, V2, and OT, located at different tissues in the body, including the uterus, the pituitary, the kidney, and the cardiovascular system. 58 AVP is also produced in normal human adrenocortical tissue as cells containing AVP were observed in both the adrenal cortex and medulla.…”