Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption
Qiong-Yu ZHANG1
Yan GUO2
Xiao-Liang JIANG3
Xing LIU3
Shu-Guang ZHAO2
Xian-Liang ZHOU1
Zhi-Wei YANG3
1.Department of Cardiology,Fuwai Hospital,National Center for Cardiovascular Disease,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China2.Emergency Department,Taihe County People's Hospital,Taihe County,Anhui Province,China3.Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical Collage(PUMC),Beijing,China
摘要：OBJECTIVES To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension(SSH).METHODS In the first part,2-month-old CCKBRfl/fl villin-Cre mice(CKO)and control CCKBRfl/fl mice(WT)were fed with normal diet(0.4％NaCl)or high salt diet(4％NaCl),separately for 6 weeks.In the rescue study,one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet.The blood pressure,biochemical indexes,and the expres-sion of small intestinal sodium transporters(NHE3,NKCC1,eNaC)was detected.The organ injury markers(MMP2/MMP9)and the histopathological changes of kidneys were observed,whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure,increased duodenal sodium ab-sorption and urinary sodium excretion,and with renal injury.The protein expression of NHE3,NKCC1 and eNaC were also sig-nificant increase in the intestine of CKO-HS mice.Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice,but no significant histopathological changes were observed. CONCLUSIONS These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic anti-hypertension effect in CCKBRfl/fl villin-Cre mice.The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.
机标关键词：hypertensionknockoutmousemodelnovelcckbr-specificintestinalover-absorption
论文发表日期：2023-07-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 538-547 )