Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy.

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.
AuthorsR W Schrier, R G Fassett, M Ohara, P Y Martin
JournalProceedings of the Association of American Physicians (Proc Assoc Am Physicians) 1998 Sep-Oct Vol. 110 Issue 5 Pg. 407-11 ISSN: 1081-650X [Print] UNITED STATES
PMID9756091 (Publication Type: Journal Article, Review)
Chemical References
  • AQP2 protein, human
  • Antidiuretic Hormone Receptor Antagonists
  • Aqp2 protein, rat
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Vasopressins
  • Animals
  • Antidiuretic Hormone Receptor Antagonists
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins (metabolism)
  • Female
  • Heart Failure (metabolism)
  • Humans
  • Liver Cirrhosis (metabolism)
  • Mechanoreceptors (metabolism)
  • Osmotic Pressure
  • Pregnancy
  • Rats
  • Vasopressins (antagonists & inhibitors, biosynthesis, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: