Therapeutic role of vasopressin receptor antagonism in patients with liver cirrhosis

Abstract

Vasopressin, or antidiuretic hormone, is a peptide hormone that is released from the posterior pituitary gland in response to changes in blood pressure and plasma osmolality. The main pathophysiological states associated with high plasma vasopressin concentrations are cirrhosis, cardiac failure and syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Pharmacological treatments for disorders of excess vasopressin secretion have been limited. However, oral bio-available selective and non-selective V(1) and V(2) receptor antagonists have recently become available for clinical use. Water retention in cirrhosis is a common problem, leading to ascites, peripheral oedema and hyponatraemia. Raised plasma vasopressin concentrations and decreased delivery of glomerular filtrate are believed to be the most important factors in the development of water retention. V(2) receptor antagonists are aquaretic agents that promote water excretion and improve hyponatraemia. Their potential role in cirrhosis has been examined in a number of recent studies that have shown increased free water clearance and serum sodium concentrations with few adverse effects. V(2) receptor antagonists represent a novel and promising new class of agent that may have major clinical utility in the treatment of patients with liver cirrhosis.

Influence of two different combination of oral contraceptive on some serum electrolytes in women

“…The fact that OC therapy reduces water consumption as reported by other researchers is a strong enough and reliable reason to hypothesize that it is the desired signal required to induce ADH secretion orchestrated by cellular dehydration for volume expansion, thus the dilution of the osmolarity. 14,[21][22][23][24] Although, the combine water retention together with secondary solute loss may result in reduction in serum sodium. 25 Hyponatremia is mediated initially by ADH-induced water retention that results in volume expansion causing dilution.…”

Consequences of Inadequate Management of Hyponatremia

“…Water is then removed to the peritubular capillaries and the systemic circulation by aquaporin-3 or 4. When AVP is removed from its receptor, aquaporin-2 is internalized, thereby reducing the osmotic water permeability [10, 11]. In normal states, escape from antidiuresis is accompanied by the downregulation of both aquaporin and V 2 receptors in the kidney [12, 13].…”

“…This receptor is expressed in the kidney and may also be present in the vascular endothelium. The V 3 receptor is expressed by cells in the anterior pituitary and is involved in the regulation of corticotropin release [10]. …”

Optimization of Vasopressin Type 2 Receptor Expression in Escherichia coli BL21

“…Production of large quantities of these receptors for drug screening and structural biology remains challenging. The vasopressin type 2 receptor (V 2 R) is a GPCR of 371 amino acids, located in nephrons, with seven transmembrane domains coupled to G protein via adenylyl cyclase and cAMP as its second messenger system (2)(3)(4)(5). Water reabsorption in the kidney collecting ducts is the main function of vasopressin, producing its anti-diuretic response (6,7).…”