title: Pathophysiology of renal fluid retention.
abstract: Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA. Robert.Schrier@UCHSC.edu
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
authors.forename: R G
authors.initials: RG
authors.lastname: Fassett
authors.forename: M
authors.initials: M
authors.lastname: Ohara
authors.forename: P Y
authors.initials: PY
authors.lastname: Martin
mesh_terms: D000818:Animals; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000502:physiology*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000502:physiology*