Diabetes, hypertension, and aging are major contributors to cardiovascular and chronic kidney disease (CKD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors have become a preferred treatment for type II diabetic patients since they have cardiorenal protective effects. However, most elderly diabetic patients also have hypertension, and the effects of SGLT2 inhibitors have not been studied in hypertensive diabetic patients or animal models. The present study examined if controlling hyperglycemia with empagliflozin, or given in combination with lisinopril, slows the progression of renal injury in hypertensive diabetic rats. Studies were performed using hypertensive streptozotocin-induced type 1 diabetic Dahl salt-sensitive (STZ-SS) rats and in deoxycorticosterone-salt hypertensive type 2 diabetic nephropathy (T2DN) rats. Administration of empagliflozin alone or in combination with lisinopril reduced blood glucose, proteinuria, glomerular injury, and renal fibrosis in STZ-SS rats without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Blood pressure and renal hypertrophy were also reduced in rats treated with empagliflozin and lisinopril. Administration of empagliflozin alone or in combination with lisinopril lowered blood glucose, glomerulosclerosis, and renal fibrosis but had no effect on blood pressure, kidney weight, or proteinuria in hypertensive T2DN rats. RBF was not altered in any of the treatment groups, and GFR was elevated in empagliflozin-treated hypertensive T2DN rats. These results indicate that empagliflozin is highly effective in controlling blood glucose levels and slows the progression of renal injury in both hypertensive type 1 and type 2 diabetic rats, especially when given in combination with lisinopril to lower blood pressure.

糖尿病、高血压和衰老是心血管疾病和慢性肾脏病 (CKD) 的主要原因。钠/葡萄糖协同转运蛋白2（SGLT2）抑制剂具有心肾保护作用，已成为II型糖尿病患者的首选治疗方法。然而，大多数老年糖尿病患者也患有高血压，而SGLT2抑制剂的作用尚未在高血压糖尿病患者或动物模型中进行研究。本研究检验了用恩格列净控制高血糖或与赖诺普利联合用药是否可以减缓高血压糖尿病大鼠肾损伤的进展。使用高血压链脲佐菌素诱导的 1 型糖尿病 Dahl 盐敏感 (STZ-SS) 大鼠和脱氧皮质酮盐高血压 2 型糖尿病肾病 (T2DN) 大鼠进行研究。单独或与赖诺普利联合使用恩格列净可降低 STZ-SS 大鼠的血糖、蛋白尿、肾小球损伤和肾纤维化，而不改变肾血流量 (RBF) 或肾小球滤过率 (GFR)。使用恩格列净和赖诺普利治疗的大鼠的血压和肾脏肥大也有所降低。单独使用恩格列净或与赖诺普利联合使用可降低高血压 T2DN 大鼠的血糖、肾小球硬化和肾纤维化，但对血压、肾脏重量或蛋白尿没有影响。任何治疗组的 RBF 均未改变，而恩格列净治疗的高血压 T2DN 大鼠的 GFR 升高。这些结果表明，恩格列净在控制血糖水平方面非常有效，并能减缓 1 型高血压和 2 型糖尿病大鼠肾损伤的进展，特别是与赖诺普利联合使用以降低血压时。