Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, Melbourne, VIC, 3004, Australia.
Iverson Health Innovation Research Institute and School of Health Science, Swinburne University of Technology, Melbourne, VIC, Australia.
Diabetologia. 2020 Jul;63(7):1424-1434. doi: 10.1007/s00125-020-05145-0. Epub 2020 May 5.
AIMS/HYPOTHESIS: We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits.
Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits.
Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05).
CONCLUSIONS/INTERPRETATION: As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.
目的/假设：我们在清醒兔糖尿病模型中确定恩格列净是否改变了肾交感神经活动（RSNA）和压力反射。
用链脲佐菌素诱导糖尿病，在接受恩格列净、胰岛素、利尿剂乙酰唑胺或 ACE 抑制剂培哚普利治疗或未治疗 1 周前后，在清醒兔中测量 RSNA、平均动脉压（MAP）和心率。
在链脲佐菌素给药 4 周后，血糖是正常对照的三倍，MAP 升高 9%（p<0.05）。与未治疗的糖尿病兔相比，恩格列净治疗 1 周可稳定降低血糖（-43%）并增加水摄入量（+49%），但不改变 RSNA、MAP 或心率。糖尿病兔的最大 RSNA 对低血压的增强作用增加了 75%（p<0.01），但心率压力反射未改变。恩格列净和乙酰唑胺降低了 RSNA 压力反射的增强作用（p<0.05），使其与非糖尿病组相似。未经处理的糖尿病兔和非糖尿病兔的去甲肾上腺素（去甲肾上腺素）溢出相似，但恩格列净和乙酰唑胺治疗的兔的去甲肾上腺素溢出增加了两倍（p<0.05）。
结论/解释：由于恩格列净可以恢复糖尿病引起的交感反射增强，这可能对糖尿病患者有益。利尿剂乙酰唑胺的类似作用表明，该机制可能涉及增加钠和水的排泄。
