Renal and cerebral RAS interaction contributes to diabetic kidney disease

American Journal of Translational Research

Lanying Li¹  Yufeng Liu² 

[1] Nephropathy Department, Tungwah Hospital of Sun Yat-sen University, Dongguan 523110, China;State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, China

关键词: Diabetic kidney disease;    renin-angiotensin system;    oxidative stress;    sympathetic nervous system;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

The diabetes mellitus has posed a grave threat on human health, and is bound to result in renal trauma by uncertain mechanisms. Increasing evidences indicated that the activation of the renin-angiotensin system plays a pivotal role during the progression of diabetic kidney disease. In streptozotocin (STZ)-induced type 1 diabetic rat model, the losartan (a selective angiotensin II type 1 (AT1) receptor antagonist) and tempol (4-Hydroxy-TEMPO, reactive oxygen species scavenger) were administrated through intracerebroventricular injection or intragastric gavage. Intracerebroventricular administration of clonidine or renal denervation was carried out to block sympathetic nerve traffic. Compared with non-diabetic rats, the reno-cerebral axis was over-activated, including activity of renin-angiotensin system (RAS), oxidative stress, and sympathetic activity in diabetic rats. Central blockade of RAS inhibited the central oxidative stress and sympathetic activity, which led to decrease of intrarenal RAS activity and oxidative stress. Meanwhile, central administration of tempol reduced brain RAS, thus downregulated renal RAS activity and oxidative stress. Importantly, oral administration by intragastric gavage of high dose of losartan and tempol achieved the same effect. The results suggested that there is a cross-talk between renal and cerebral RAS/reactive oxygen species, contributing to the progression of diabetic kidney disease. The subfornical organ, paraventricular nucleus, and supraoptic nucleus in the forebrain also play a key role in development and progression of renal trauma through reno-cerebral reflex axis.

【 授权许可】

CC BY-NC