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.
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Authors | Katharina Hopp, Xiaofang Wang, Hong Ye, María V Irazabal, Peter C Harris, Vicente E Torres |
Journal | American journal of physiology. Renal physiology
(Am J Physiol Renal Physiol)
Vol. 308
Issue 3
Pg. F261-6
(Feb 01 2015)
ISSN: 1522-1466 [Electronic] United States |
PMID | 25503729
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 the American Physiological Society. |
Chemical References |
- Receptors, Vasopressin
- Arginine Vasopressin
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Topics |
- Animals
- Arginine Vasopressin
(metabolism)
- Disease Models, Animal
- Drinking
(physiology)
- Hypodermoclysis
(adverse effects)
- Kidney
(metabolism, pathology)
- Mice, Inbred C57BL
- Mice, Transgenic
- Polycystic Kidney Diseases
(metabolism)
- Rats
- Receptors, Vasopressin
(metabolism)
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