Intestinal Cckbr -specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption

• Published in: Journal of geriatric cardiology : JGC 2023-07, Vol.20 (7), p.538-547
• Main Authors: Zhang, Qiong-Yu, Guo, Yan, Jiang, Xiao-Liang, Liu, Xing, Zhao, Shu-Guang, Zhou, Xian-Liang, Yang, Zhi-Wei
• Format: Article
• Language: English
• ISSN: 1671-5411
• DOI: 10.26599/1671-5411.2023.07.001

To investigate the value of CCKBR villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). In the first part, 2-month-old CCKBR villin-Cre mice (CKO) and control CCKBR 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 expression 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. The CCKBR villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBR villin-Cre mice, but no significant histopathological changes were observed. These results support a crucial role of intestinal deficiency on SSH development and the diuretic antihypertension effect in CCKBR villin-Cre mice. The CCKBR villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.