Insufficient hypothalamic angiotensin-converting enzyme 2 is associated with hypertension in SHR rats.

Kun Wang,Yuanshu Zhang,Yuanyuan Xu,Weiwei Yang

doi:10.18632/oncotarget.15666

Abstract

Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin system (RAS), which is implicated in the pathogenesis of hypertension and other cardiovascular diseases. In this study we investigated the expression of ACE2 in the hypothalamus and pituitary tissues and its relationship to hypertension by comparing them in male WKY and SHR rats. We observed that the plasma levels of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and aldosterone (ALD) were all lower in SHR than WKY rats (P<0.05), whereas plasma angiotensin II (AngII) levels were higher in SHR rats (P<0.05). Levels of ACE mRNA and protein were higher in the hypothalamus of SHR than WKY rats (P<0.05). By contrast, hypothalamic expression of ACE2 protein was lower in SHR rats (P<0.05), despite comparable mRNA levels in SHR and WKY rats. There were no differences in the expression levels of ACE, ACE2, AT1 or Mas mRNA in the pituitaries of SHR and WKY rats (P>0.05). These results suggest that insufficiency of hypothalamic ACE2 is associated with hypertension in SHR rats.

Highlights

The role of the renin–angiotensin system (RAS) in the pathogenesis of hypertension and other cardiovascular diseases is widely acknowledged [1]
Unpaired t-test indicated that plasma corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and ALD levels decreased significantly in spontaneously hypertensive rats (SHR) group, In contrast, Ang II level in plasma increased markedly
Recent data indicates that angiotensin-converting enzyme 2 (ACE2) has an opposing effect to that of angiotensin-converting enzyme (ACE) which could have novel implications regarding the role of RAS in hypertension and cardiovascular diseases [23, 24, 25]

Summary

Introduction

The role of the renin–angiotensin system (RAS) in the pathogenesis of hypertension and other cardiovascular diseases is widely acknowledged [1]. The traditional view that Ang II is the sole key effector peptide of the RAS has been questioned by the subsequent discovery of angiotensin-converting enzyme 2 (ACE2) [2, 3] and the growing evidence for a physiological role for Angiotensin-(1–7) [4]. Cardiac ACE2 was suppressed and ACE upregulated in the SHR compared to WKY rats [8]. It was implicated in pro-inflammatory cytokines (PICs) such as tumor necrosis factor (TNF)-a, interleukin (IL)-6, and IL-1b both centrally and in the periphery [9, 10]

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