Vasopressin: a new target for the treatment of heart failure.
BACKGROUND
Arginine vasopressin is a peptide hormone that modulates a number of processes implicated in the pathogenesis of heart failure. Numerous vasopressin antagonists are currently under development for the treatment of this syndrome.


METHODS
Preclinical and clinical data describing the effects of vasopressin and the vasopressin antagonists on both normal physiology and heart failure were reviewed.


RESULTS
Through activation of V(1a) and V(2) receptors, vasopressin regulates various physiological processes including body fluid regulation, vascular tone regulation, and cardiovascular contractility. Vasopressin synthesis is significantly and chronically elevated in patients with heart failure despite the volume overload and reductions in plasma osmolality often observed in these patients. Vasopressin also appears to adversely effect hemodynamics and cardiac remodeling, while potentiating the effects of norepinephrine and angiotensin II. The selective V(2) and dual V(1a)/V(2) receptor antagonists tolvaptan and conivaptan, respectively, substantially increase free water excretion and plasma osmolality, reduce body weight, improve symptoms of congestion, and moderately increase serum sodium concentrations in patients with heart failure who present with symptoms of fluid overload. Tolvaptan effectively normalizes serum sodium concentrations in hyponatremic heart failure patients. Conivaptan significantly reduces pulmonary capillary wedge pressure without affecting systemic vascular resistance or cardiac output. The clinical significance of V(1a) receptor antagonism requires further investigation.


CONCLUSIONS
Current preclinical and clinical findings with the vasopressin antagonists appear promising, however further evaluation in phase III clinical trials is necessary to define the role of vasopressin antagonism in the treatment of heart failure.
Lee
Craig R
CR
School of Pharmacy, University of North Carolina at Chapel Hill, 27599-7075, USA.
Watkins
Michael L
ML
Patterson
J Herbert
JH
Gattis
Wendy
W
O'connor
Christopher M
CM
Gheorghiade
Mihai
M
Adams
Kirkwood F
KF
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000097:blood / Q000502:physiology; D001826:Body Fluids / Q000502:physiology; D002303:Cardiac Output, Low / Q000188:drug therapy; D006332:Cardiomegaly / Q000209:etiology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D017483:Receptors, Vasopressin / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D018377:Neurotransmitter Agents; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin