title: Effects of hydration in rats and mice with polycystic kidney disease.
abstract: 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.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hopp
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: María V
authors.initials: MV
authors.lastname: Irazabal
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota torres.vicente@mayo.edu.
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D004195:Disease Models, Animal; D004326:Drinking / Q000502:physiology; D055103:Hypodermoclysis / Q000009:adverse effects; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin
keywords: cAMP; cyclic nucleotide phosphodiesterase; hydration; polycystic kidney disease; vasopressin