The renin-angiotensin-aldosterone system in heart failure for the non-specialist: the past, the present and the future

Abstract

Heart failure is one of the major public health challenges facing the Western world. Its prevalence is increasing as the population ages and modern techniques are implemented to manage cardiac disease. In response, there has been a sustained effort to develop novel strategies to address the high levels of associated morbidity and mortality. Indeed, agents that target the renin-angiotensin-aldosterone system (RAAS) have transformed the way in which we manage heart failure. Despite this, mortality in heart failure is poorer than in many malignancies and a large burden of morbidity and recurrent hospitalisation remains. Here, we review the role of RAAS modulation within the field of systolic heart failure. In particular, we provide practical guidance on using current RAAS blockade agents and focus on the recent emergence of new agents that promise additional substantial benefit to those living with left ventricular systolic dysfunction.

The Role of Renal Vascular Reactivity in the Development of Renal Dysfunction in Compensated and Decompensated Congestive Heart Failure

“…Altogether our findings support the notion that CHF is not a purely hemodynamic disorder that markedly affects renal hemodynamics. Thus neurohormonal activation of the RAS and SNS are important determinants of further CHF progression [16,17,[20][21][22][24][25][26][27][28].…”

“…However, the role of increased ANG II concentrations and actions was not unequivocally confirmed and most probably is not the sole causative factor in the development of renal dysfunction in CHF. More likely, the mechanism responsible for the reduction of RBF involves intrarenal interaction between the RAS and other vasoactive system(s) [14,15,19,21,[23][24][25][26][27][28].…”

Neurohumoral Pathway in Heart Failure

“…Reports showed that during heart failure, the activity of ACE is increased as shown that the tissue expression increased in the myocardium. This further supported with the increased in Angiotensin II activity during heart failure that stimulates vasoconstriction, cellular growth and tissue remodeling, extracellular matrix synthesis which may exacerbate the fibrosis in heart failure condition 3,6 . There are two opposing receptors that binds to Angiotensin II and mediates its activity, Angiotensin recepor type 1 and Angiotensin receptor type 2.…”

“…In addition, in the in vitro and in vivo model, the RAAS has plaucible function in the cellular and tissue remodeling as well as the increase response in inflamatory process. Thus, the inapporpriate response of the RAAS during certain pathological condition will lead to tissue remodeling and dysfunction in cardiovascular system 6 .…”

O envolvimento do sistema Renina-Angiotensina nas disfunções cardiovasculares e seus recursos farmacológicos

“…A monoterapia atual, apesar de eficiente, é limitada e apresenta falhas 4 . Sendo assim, foi considerada o uso da multiterapia com o objetivo de tornar o bloqueio do SRA mais satisfatório 4, 20,27 .Um dos objetivos da combinação do IECA com ARA II é impedir a geração da Ang II por vias alternativas e assim proporcionar uma inibição mais completa sobre o SRA 6,8 .…”