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Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population
and Attenuates Salt-Sensitive Hypertension in Dahl S Rats
#MMPMID28693025
Wang Z
; Zhu Q
; Wang W
; Yi F
; Li PL
; Boini KM
; Li N
Cell Physiol Biochem
2017[]; 42
(3
): 1264-1273
PMID28693025
show ga
BACKGROUND: Our previous study has detected a stem cell deficiency in the renal
medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion
of valproic acid (VA), an agent known to stimulate the stem cell function,
attenuated salt-sensitive hypertension in Dahl S rats. METHODS: Uninephrectomized
Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla
and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were
analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium
excretion and blood pressure were measured. RESULTS: VA significantly increased
the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem
cell marker. The number of CD133+ cells was significantly increased in the renal
medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA
level of proinflammatory factors interleukin-1? and interleukin-6 were blocked in
VA-treated rats. Functionally, sodium excretion in response to the blood pressure
increase and acute sodium loading was significantly enhanced, sodium retention
attenuated, high salt-induced increase of blood pressure reduced in VA-treated
rats. CONCLUSION: Activation of stem cell function by VA inhibits the activation
of proinflammatory factors and attenuates salt-sensitive hypertension in Dahl S
rats.
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