Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes
Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes
复制标题
DOI：
10.1007/s00125-020-05145-0
复制
发表时间：
2020-05-05
期刊：
影响因子：
8.2
通讯作者：
Head, Geoffrey A.
中科院分区：
文献类型：
--
作者：
Gueguen, Cindy;Burke, Sandra L.;Head, Geoffrey A.
目的/假设我们在清醒的兔糖尿病模型中确定了依帕格列酮是否改变了肾交感神经活动(RSNA)和压力感受器反射。方法采用四氧嘧啶诱发清醒兔糖尿病模型，分别于治疗前、治疗1周后及不治疗前、后测定RSNA、平均动脉压(MAP)和心率。结果服用四氧嘧啶4周后，血糖和平均动脉压较非糖尿病对照组高3倍，平均动脉压高9%(p<；0.05)。与未经治疗的糖尿病兔相比，接受埃帕利福秦治疗一周后，血糖稳定下降(-43%)，摄水量增加(+49%)，但没有改变RSNA、MAP或心率。糖尿病兔对低血压的最大RSNA增加了75%(p<；0.01)，但心率压力感受性反射没有改变。依帕格列秦和乙酰唑胺降低了RSNA压力感受器反射的增强(p<；0.05)，与非糖尿病组相似。去甲肾上腺素(去甲肾上腺素)溢出效应在未治疗的糖尿病兔和非糖尿病兔中相似，但在依帕格列酮和乙酰唑胺治疗的兔中，去甲肾上腺素(去甲肾上腺素)外溢增加了两倍(p<；0.05)。结论/解释为依帕格列酮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，其机制可能涉及增加钠和水的排泄。
Aims/hypothesis We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. Methods 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. Results 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.