PATHOPHYSIOLOGY OF RENAL FLUID RETENTION

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.