A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats
A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats
复制标题
DOI：
10.1038/hr.2016.2
复制
发表时间：
2016-06-01
影响因子：
5.4
通讯作者：
Nishiyama, Akira
中科院分区：
文献类型：
--
作者：
Takeshige, Yui;Fujisawa, Yoshihide;Nishiyama, Akira
研究人员进行了研究，以检查选择性钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂恩格列净 (empagliflozin) 对盐处理的肥胖大冢龙埃文斯德岛脂肪 (OLETF) 大鼠尿钠排泄和昼夜血压的影响。 15 周大的肥胖 OLETF 大鼠接受 1% NaCl（饮用水中）和媒介物（0.5% 羧甲基纤维素，n=10）或恩格列净（每天 10 mg kg(-1)，口服，n=11）治疗 5 周。通过遥测系统连续测量血压。分别通过口服葡萄糖耐量试验和高盐激发试验评估葡萄糖代谢和尿钠排泄。媒介物治疗的 OLETF 大鼠出现非杓型血压升高，伴有葡萄糖不耐受和胰岛素抵抗。与媒介物治疗的动物相比，恩格列净治疗的 OLETF 大鼠的尿葡萄糖排泄量增加了约 1000 倍，并改善了葡萄糖代谢和胰岛素抵抗。此外，恩格列净通过将昼夜节律正常化为北斗型来防止血压升高，这与尿钠排泄增加有关。这些数据表明，恩格列净对高盐肥胖状态下的葡萄糖稳态和高血压产生有益作用。
Studies were performed to examine the effects of the selective sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on urinary sodium excretion and circadian blood pressure in salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Fifteen-week-old obese OLETF rats were treated with 1% NaCl (in drinking water), and vehicle (0.5% carboxymethylcellulose, n=10) or empagliflozin (10 mg kg(-1) per day, p.o., n=11) for 5 weeks. Blood pressure was continuously measured by telemetry system. Glucose metabolism and urinary sodium excretion were evaluated by oral glucose tolerance test and high salt challenge test, respectively. Vehicle-treated OLETF rats developed non-dipper type blood pressure elevation with glucose intolerance and insulin resistance. Compared with vehicle-treated animals, empagliflozin-treated OLETF rats showed an approximately 1000-fold increase in urinary glucose excretion and improved glucose metabolism and insulin resistance. Furthermore, empagliflozin prevented the development of blood pressure elevation with normalization of its circadian rhythm to a dipper profile, which was associated with increased urinary sodium excretion. These data suggest that empagliflozin elicits beneficial effects on both glucose homeostasis and hypertension in salt-replete obese states.