Increased water intake decreases progression of polycystic kidney disease in the PCK rat.
Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.
Nagao
Shizuko
S
Education and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi, Japan.
Nishii
Kazuhiro
K
Katsuyama
Makoto
M
Kurahashi
Hiroki
H
Marunouchi
Tohru
T
Takahashi
Hisahide
H
Wallace
Darren P
DP
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D007690:Polycystic Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D014867:Water / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D014867:Water