Clinical Perspectives and Fundamental Aspects of Local Cardiovascular and Renal Renin-Angiotensin Systems

Walmor C De Mello,Edward D Frohlich

doi:10.3389/fendo.2014.00016

Abstract

Evidence for the potential role of organ specific cardiovascular renin–angiotensin systems (RAS) has been demonstrated experimentally and clinically with respect to certain cardiovascular and renal diseases. These findings have been supported by studies involving pharmacological inhibition during ischemic heart disease, myocardial infarction, cardiac failure; hypertension associated with left ventricular ischemia, myocardial fibrosis and left ventricular hypertrophy; structural and functional changes of the target organs associated with prolonged dietary salt excess; and intrarenal vascular disease associated with end-stage renal disease. Moreover, the severe structural and functional changes induced by these pathological conditions can be prevented and reversed by agents producing RAS inhibition (even when not necessarily coincident with alterations in arterial pressure). In this review, we discuss specific fundamental and clinical aspects and mechanisms related to the activation or inhibition of local RAS and their implications for cardiovascular and renal diseases. Fundamental aspects involving the role of angiotensins on cardiac and renal functions including the expression of RAS components in the heart and kidney and the controversial role of angiotensin-converting enzyme 2 on angiotensin peptide metabolism in humans, were discussed.

Highlights

The presence of local organ specific renin–angiotensin systems (RAS) has been demonstrated for the heart, large arteries and arterioles, kidneys, and other organs and their activation lead to structural and functional changes, which are independent of those elicited by the classical renin–angiotensin endocrine system [1,2,3,4]
We present several clinical circumstances involving certain cardiovascular diseases, which support the notion that the activation of local RAS plays an important role on the mechanisms of these pathological conditions
SUMMARY Recent findings that Ang angiotensin II (II) can be hydrolyzed by angiotensin-converting enzyme 2 (ACE2) and neprisylin as well the evidence of new receptors for Ang (IV), Ang [1,2,3,4,5,6,7], and Ang III, and the possibility that Ang [1,2,3,4,5,6,7,8,9,10,11,12] might be the mother of all angiotensins are other evidences of how complex is the RAS

Summary

INTRODUCTION

The presence of local organ specific renin–angiotensin systems (RAS) has been demonstrated for the heart, large arteries and arterioles, kidneys, and other organs and their activation lead to structural and functional changes, which are independent of those elicited by the classical renin–angiotensin endocrine system [1,2,3,4]. We present several clinical circumstances involving certain cardiovascular diseases, which support the notion that the activation of local RAS plays an important role on the mechanisms of these pathological conditions. These vignettes cited involve renal diseases because the renal glomerular and arteriolar alterations contribute to the development and progression of end-stage renal disease (ESRD)

CLINICAL CIRCUMSTANCES

Findings

De Mello and Frohlich