Arginine Vasopressin Antagonists for the Treatment of Heart Failure and Hyponatremia

Abstract

A rginine vasopressin has attracted attention as a potentially important neurohormonal mediator of the heart failure (HF) syndrome and hyponatremic states in humans 1 because vasopressin influences renal handling of free water, vasoconstriction, and myocyte biology. 2,3 Several vasopressin antagonists are under development, 4 and one of these agents, conivaptan, recently received US Food and Drug Administration approval for short-term intravenous treatment in patients with euvolemic or hypervolemic hyponatremia. The Role of Vasopressin in HF and HyponatremiaA neurohypophysial hormone, vasopressin (also called antidiuretic hormone [ADH]), affects free water reabsorption by the kidney, body fluid osmolality, blood volume, vasoconstriction, and myocardial contractile function. 2,3 Vasopressin is synthesized by neurosecretory cells located predominantly in the supraoptic and paraventricular hypothalamic nuclei. These neurons have axons terminating in the neural lobe of the posterior pituitary (neurohypophysis) that release vasopressin and oxytocin. 5

Mortality risk prediction in COPD by a prognostic biomarker panel

“…These were expected to capture not only inflammation but also other systemic repercussions of the disease as well as associated comorbidities. While ADM is associated with inflammation, tissue remodelling and hypoxia, AVP modulates fluid homeostasis and oxidative stress, and ANP is related to cardiac dysfunction [18,19,45]. Hypoxia leads to ADM upregulation through the hypoxia inducible factor-1 pathway, which interacts with nuclear factor-kB to promote the expression of inflammatory genes [15,[46][47][48].…”

“…In COPD airway inflammation, ADM may act primarily to promote tissue repair and maintain microvascular function [16,17]. Arginine vasopressin (AVP) is a potent vasoconstrictor that promotes water retention and plays a role in the body's stress response by stimulating adrenocorticotrophic hormone secretion [18]. AVP also seems to reduce bronchial obstruction, shunt fraction and oedema formation, thereby improving gas exchange, reversing myocardial dysfunction, reducing plasma levels of nitrogen oxides and limiting pulmonary tissue concentrations of reactive nitrogen species [19].…”

Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology

“…In addition to plasma osmolality, non-osmotic factors, such as intra-cardiac pressures, intra-arterial pressures, angiotensin II, pain, and adrenergic (α2) central nervous stimuli can also influence AVP secretion [36]. Although non-osmotic mechanisms do not usually play an important role in healthy individuals, edematous states are characterized by a shift in regulation towards predominance of non-osmotic over the physiological osmotic stimuli.…”

Serum copeptin level can be a helpful biomarker in evaluation of myocardial perfusion scintigraphy results

“…Opposite to vasopressin which has a half-life of 10-20 min, copeptin can be detected in the circulation for days [15]. Serum vasopressin level has been shown to be increased in heart failure, septic shock, myocardial infarction and other endogenous stress conditions [16][17][18].…”