Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
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DOI：
10.1016/j.biopha.2021.112246
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发表时间：
2021-10-01
影响因子：
7.5
通讯作者：
Vaneckova, Ivana
中科院分区：
文献类型：
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作者：
Hojna, Silvie;Rauchova, Hana;Vaneckova, Ivana
新型抗糖尿病药物格列净可抑制肾近端小管中促进葡萄糖和钠排泄的钠-葡萄糖转运蛋白-2。这不仅导致血糖控制的显著改善，而且还导致糖尿病患者和实验模型中血压和体重的降低。我们研究了这些有益的效果是否也可以在非糖尿病高血压模型中实现，即在Ren-2转基因大鼠（TGR）中。成年6月龄高血压TGR及其血压正常对照组（汉诺威Sprague-Dawley大鼠）未接受治疗或接受恩格列净（10 mg/kg/天）治疗2个月。在实验过程中，通过遥测血压监测，肾脏参数以及心脏功能超声心动图进行了分析。在研究结束时，研究了主要血管活性系统对血压维持的贡献。还分析了代谢参数以及氧化应激和炎症的标志物。恩格列净对TGR患者的血糖水平无影响，但可部分降低血压。尽管恩格列净给药TGR的摄食量显著高于未给药动物，但其体重以及附睾和肾周脂肪量均降低。恩格列净对蛋白尿无影响，但可降低血浆尿素，减轻肾脏氧化应激，暂时增加尿尿素排泄。恩格列净治疗还改善了几个代谢（肝甘油三酯、非酯化脂肪酸、胰岛素）和炎症（TNF-α、瘦素）参数。相比之下，超声心动图未显示恩格列净对心脏功能的任何影响。总之，恩格列净在非糖尿病高血压模型中也发挥了有益的降压、抗炎和代谢作用。
The new antidiabetic drugs, gliflozins, inhibit sodium-glucose transporter-2 in renal proximal tubules promoting glucose and sodium excretion. This leads not only to a significant improvement of glucose control but also to the reduction of blood pressure and body weight in both diabetic patients and experimental models. We examined whether these beneficial effects can also be achieved in a non-diabetic hypertensive model, namely in Ren-2 transgenic rats (TGR). Adult 6-month-old hypertensive TGR and their normotensive controls (Hannover Sprague-Dawley rats), were either untreated or treated with empagliflozin (10 mg/kg/day) for two months. Telemetric blood pressure monitoring, renal parameters as well as cardiac function via echocardiography were analyzed during the experiment. At the end of the study, the contribution of major vasoactive systems to blood pressure maintenance was studied. Metabolic parameters and markers of oxidative stress and inflammation were also analyzed. Empagliflozin had no effect on plasma glucose level but partially reduced blood pressure in TGR. Although food consumption was substantially higher in empagliflozin-treated TGR compared to the untreated animals, their body weight and the amount of epididymal and perirenal fat was decreased. Empagliflozin had no effect on proteinuria, but it decreased plasma urea, attenuated renal oxidative stress and temporarily increased urinary urea excretion. Several metabolic (hepatic triglycerides, non-esterified fatty acids, insulin) and inflammatory (TNF-alpha, leptin) parameters were also improved by empagliflozin treatment. By contrast, echocardiography did not reveal any effect of empagliflozin on cardiac function. In conclusion, empagliflozin exerted beneficial antihypertensive, anti-inflammatory and metabolic effects also in a non-diabetic hypertensive model.