Effects of hydration in rats and mice with polycystic kidney disease

Am J Physiol Renal Physiol. 2015 Feb 1;308(3):F261-6. doi: 10.1152/ajprenal.00345.2014. Epub 2014 Dec 10.


Vasopressin and V2 receptor signaling promote polycystic kidney disease (PKD) progression, raising the question whether suppression of vasopressin release through enhanced hydration can delay disease advancement. Enhanced hydration by adding 5% glucose to the drinking water has proven protective in a rat model orthologous to autosomal recessive PKD. We wanted to exclude a glucose effect and explore the influence of enhanced hydration in a mouse model orthologous to autosomal dominant PKD. PCK rats were assigned to normal water intake (NWI) or high water intake (HWI) groups achieved by feeding a hydrated agar diet (HWI-agar) or by adding 5% glucose to the drinking water (HWI-glucose), with the latter group used to recapitulate previously published results. Homozygous Pkd1 R3277C (Pkd1(RC/RC)) mice were assigned to NWI and HWI-agar groups. To evaluate the effectiveness of HWI, kidney weight and histomorphometry were assessed, and urine vasopressin, renal cAMP levels, and phosphodiesterase activities were measured. HWI-agar, like HWI-glucose, reduced urine vasopressin, renal cAMP levels, and PKD severity in PCK rats but not in Pkd1(RC/RC) mice. Compared with rat kidneys, mouse kidneys had higher phosphodiesterase activity and lower cAMP levels and were less sensitive to the cystogenic effect of 1-deamino-8-d-arginine vasopressin, as previously shown for Pkd1(RC/RC) mice and confirmed here in Pkd2(WS25/-) mice. We conclude that the effect of enhanced hydration in rat and mouse models of PKD differs. More powerful suppression of V2 receptor-mediated signaling than achievable by enhanced hydration alone may be necessary to affect the development of PKD in mouse models.

Keywords: cAMP; cyclic nucleotide phosphodiesterase; hydration; polycystic kidney disease; vasopressin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / metabolism*
  • Disease Models, Animal
  • Drinking / physiology
  • Hypodermoclysis / adverse effects
  • Kidney / metabolism
  • Kidney / pathology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Polycystic Kidney Diseases / metabolism*
  • Rats
  • Receptors, Vasopressin / metabolism*


  • Receptors, Vasopressin
  • Arginine Vasopressin