In-Depth Topic Review

Hyponatremia, Arginine Vasopressin Dysregulation, and Vasopressin Receptor Antagonism
Amit Rai^a, Adam Whaley-Connell^a, Samy McFarlane^b, James R. Sowers<sup>c

a</sup>Departments of Internal Medicine, Division of Nephrology, University of Missouri-Columbia School of Medicine, and Harry S. Truman VA Medical Center, Columbia, Mo.,
^bState University of New York, Brooklyn, N.Y., and
^cUniversity of Arizona Diabetes Center, Tucson, Ariz., USA

Address of Corresponding Author

Am J Nephrol 2006;26:579-589 (DOI: 10.1159/000098028)

  Key Words

• Aquaporins
• Arginine vasopressin
• Vasopressin-receptor antagonist, SIADH
• Hyponatremia, vasopressin dysregulation

  Abstract

Hyponatremia is often associated with arginine vasopressin (AVP) dysregulation that is regulated by the hypothalamo-neurohypophyseal tract in response to changes in plasma osmolality, commonly in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Potentially lethal complications of hyponatremia most frequently involve the central nervous system and include anorexia, fatigue, lethargy, delirium, seizures, hypothermia and coma, and require prompt treatment. Chronic hyponatremia also complicates patient care and is associated with increased morbidity and mortality, particularly among patients with congestive heart failure. Conventional treatments for hyponatremia (e.g. fluid restriction, diuretic treatment, and sodium replacement) may not be effective in all patients and can lead to significant adverse events. Preclinical and clinical trial results have shown that AVP receptor antagonism is a promising approach to the treatment of hyponatremia that directly addresses the effects of increased AVP and consequent decreased aquaresis, the electrolyte-sparing excretion of free water. Agents that antagonize V₂ receptors promote aquaresis and can lead to increased serum sodium. Dual-receptor antagonism, in which both V₂ and V_1A receptors are blocked, may provide additional benefits in patients with hyponatremia.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Prof. James R. Sowers, MD
University of Arizona Diabetes Center
Diabetes Research Center, 1656 E Mabel St, PO Box 245218
Tuscon, AZ 85724-5218 (USA)
E-Mail sowersj@email.arizona.edu

  Article Information

Received: October 19, 2006
Accepted: November 13, 2006
Published online: December 14, 2006
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 1, Number of References : 85