Endocrine Abstracts (2012) 29 P316

Dysregulation of tissue renin-angiotensin-aldosterone system in obese hypertensive rats

Y. Takeda, Y. Cheng, M. Demura, T. Yoneda, M. Kometani, T. Sawamura & S. Karashima

Kanazawa University, Kanazawa, Japan.

The activation of local renin–angiotensin–aldosterone system (RAAS) plays a pivotal role in the overall pathophysiology of the cardiovascular and renal diseases. Aldosterone can activate local renin and angiotensin converting enzyme (ACE). However, the effects of blockade of aldosterone on tissue RAAS including (pro)renin receptor and ACE2 are unclear in obese hypertensive rats induced by high-salt diet. Obese Zucker rats (ZOR) were fed with normal or high-salt diet for 8 weeks, and treated with eplerenone (100 mg/kg per day). ZOR fed a high-salt diet increased blood pressure (BP), kidney weight, urinary albumin excretion and urinary angiotensinogen excretion. Under these conditions, the rats exhibited decreased PRA and plasma aldosterone concentration and concomitant with increased expression of renal (pro)renin receptor protein and mRNA levels of angiotensinogen and ACE in the kidney. Treatment with eplerenone in ZOR fed a high-salt diet was associated with significant improvements in BP, kidney weight, urinary albumin excretion, urinary angiotensinogen excretion and decreased renal (pro)renin receptor protein expression and angiotensinogen and ACE mRNA levels. These results suggest that a high-salt diet increased renal RAAS, while blockade of aldosterone attenuated renal injuries by decreasing the activity of tissue RAAS in obese hypertension.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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