The Role of Renin–Angiotensin–Aldosterone System and Its New Components in Arterial Stiffness and Vascular Aging

Abstract

Many cardiovascular diseases present renin-angiotensin-aldosterone system (RAAS) hyperactivity as an important pathophysiological mechanism to be target in the therapeutic approaches. Moreover, arterial stiffness is currently considered as a new independent risk factor for cardiovascular disease in different clinical conditions, including hypertension and chronic kidney disease. In fact, excessive stimulation of angiotensin type 1 (AT1) receptors, as well as mineralocorticoid receptors, results in cellular growth, oxidative stress and vascular inflammation, which may lead to arterial stiffness and accelerate the process of vascular aging. In the last decades, a vasoprotective axis of the RAAS has been discovered, and now it is well established that new components with antioxidant and anti-inflammatory properties play important roles promoting vasodilation, natriuresis and reducing collagen deposition, thus attenuating arterial stiffness and improving endothelial function. In this review, we will focus on these pathophysiological mechanisms and the relevance of RAAS inhibition by different strategies to increase arterial compliance and to decelerate vascular aging.

Blockade of angiotensin AT1 receptors prevents arterial remodelling and stiffening in iron‐overloaded rats

“…As identified in the protocols for vascular reactivity under in vitro AT 1 receptor blockade, these authors suggested that reduced NO and elevated ROS, due to AT 1 receptor activation could play a role in the genesis of vascular functional and structural remodelling in the rat model of iron‐overload. In fact, the mechanism by which drugs that inhibit the RAS attenuate or reverse vascular remodelling is related to the modulation of growth‐promoting, pro‐oxidant, and pro‐inflammatory actions of Ang II and thereby improving the arterial compliance, all independent of BP reduction (Brassard, Amiri, & Schiffrin, ; Janić, Lunder, & Sabovič, ; Neves, Cunha, Cunha, Gismondi, & Oigman, ; Ng et al, ; Shahin et al, ; Zhu et al, ). Consistent with these findings, the blockade of AT 1 receptors in vivo, was capable of preventing aortic deposition of collagen and stiffening also in the iron‐overload model.…”

60 years towards definition of dyscirculatory (vascular) encephalopathy: can we put new wine into old wineskins?

“…Показано, что артериальная гипертензия, являющаяся одним из основных факторов развития ДЭП, не только изменяет структуру церебральных сосудов, вызывая гипертрофию и ремоделирование сосудистой стенки, способствует развитию атеросклероза крупных сосудов и липогиалиноза мелких сосудов, но и может блокировать феномен функциональной гиперемии. Это сопровождается снижением прироста перфузии в теменной коре и таламусе при выполнении когнитивных тестов, что коррелирует с ухудшением их результатов [20][21][22].…”

Utility of obesity and metabolic dyslipidemia (a non‐insulin based determinate of the metabolic syndrome and insulin resistance) in predicting arterial stiffness

“…23,24 Endothelial stiffness and whole vessel stiffness are also promoted by activation of the systemic and local reninangiotensin-aldosterone axis as well as vascular mineralocorticoid receptor activation and increased expression of angiotensin II type 1 receptors leading to vessel wall hypertrophy and fibrosis, which reduce arterial elasticity. 24,25…”

“…IR states and the resultant endothelial stiffness are also characterized by an imbalance between endothelial production of important opposing regulators of arterial stiffness, such as NO and endothelin‐1, whose levels are reduced and increased, respectively . Endothelial stiffness and whole vessel stiffness are also promoted by activation of the systemic and local renin‐angiotensin‐aldosterone axis as well as vascular mineralocorticoid receptor activation and increased expression of angiotensin II type 1 receptors leading to vessel wall hypertrophy and fibrosis, which reduce arterial elasticity …”