Takeshige Yui, Fujisawa Yoshihide, Rahman Asadur, Kittikulsuth Wararat, Nakano Daisuke, Mori Hirohito, Masaki Tsutomu, Ohmori Koji, Kohno Masakazu, Ogata Hiroaki, Nishiyama Akira
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Division of Nephrology, Department of Medicine, Showa University School of Medicine, Yokohama, Japan.
Hypertens Res. 2016 Jun;39(6):415-22. doi: 10.1038/hr.2016.2. Epub 2016 Jan 28.
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.
开展了多项研究，以考察选择性钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂恩格列净对盐处理的肥胖大冢长-艾-托（OLETF）大鼠尿钠排泄及昼夜血压的影响。对15周龄的肥胖OLETF大鼠给予1% NaCl（溶于饮用水中），并分别给予赋形剂（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），持续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。给予赋形剂的OLETF大鼠出现非勺型血压升高，并伴有葡萄糖不耐受和胰岛素抵抗。与给予赋形剂的动物相比，给予恩格列净的OLETF大鼠尿葡萄糖排泄增加约1000倍，葡萄糖代谢和胰岛素抵抗得到改善。此外，恩格列净可预防血压升高的发生，其昼夜节律恢复正常呈勺型，这与尿钠排泄增加有关。这些数据表明，恩格列净对盐充足的肥胖状态下的葡萄糖稳态和高血压均有有益作用。
