Central to a unifying hypothesis of body fluid regulation is maintenan
ce of arterial circulatory integrity. This may be disturbed by arteria
l underfilling, either from reduction in cardiac output or by peripher
al arterial vasodilation. In cardiac failure (CF), cardiac output fall
s and the nonosmotic release of arginine vasopressin (AVP) and express
ion of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor an
tagonists 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 a
quaporin-2 (AQP-2) water channels. In conditions associated with perip
heral vasodilation, such as cirrhosis, nonosmotic release of AVP also
occurs, and AQP-2 gene expression in the rat kidney is up-regulated. I
n cirrhosis, nitric oxide-mediated vasodilation occurs early prior to
water retention. V2 antagonists reverse the latter. In normal pregnanc
y, plasma AVP is relatively high for the degree of hypoosmolality. Pre
gnant rats up-regulate AQP-2 in the renal papilla, an effect reversed
by V2 receptor antagonists. This supports the hypothesis that AVP is a
n important mediator of renal water retention in pregnancy. In summary
, AVP-mediated water retention through collecting duct AQP-2 water cha
nnels is important in both low-output CF and high-output states such a
s cirrhosis and pregnancy. V2 receptor antagonists reverse the water r
etention and down-regulate AQP-2 water channels.