Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights from a Human Model Opposite to Hypertension

Abstract

Insights into the Angiotensin II (Ang II) signalling pathways have been provided by extensive studies using Bartter's/Gitelman's syndromes patients. These syndromes are characterized by activation of the renin-angiotensin-aldosterone system but do not develop hypertension and cardiovascular remodelling, therefore represent a mirror image of hypertension and clinically manifest themselves as the opposite of hypertension. The short and the long-term signalling of Ang II remain an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications, such as cardiovascular remodelling and atherogenesis. In particular the long-term signalling of Ang II is involved in the pathophysiology of cardiovascular-renal remodelling, inflammatory and hypertrophic responses in which the relationship between RhoA/Rho kinase pathway and NO system plays a crucial role. This review reports the results of our studies in Bartter's and Gitelman's syndromes to get better insight these processes and the role of Ang II signaling. The information obtained from the studies in Bartter's/Gitelman's patients can, in fact, clarify, confirm or be used to gather more general data on the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could contribute to identify additional potential significant targets of therapy.

From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease

“…Moreover, AT1R activation mediates the balance between the intracellular levels of nitric oxide (NO) and calcium through the PI3K/Akt pathway. The suppression of endothelial nitric oxide synthase (eNOS) and increasing cytosol calcium levels through inositol 1,4,5-trisphosphate (IP3) elevate the resistance of efferent arterioles and disrupt the autoregulation of afferent arterioles, which eventually leads to glomerular hyperfiltration and sclerosis [172,174,175] (Figure 3). Aldosterone is a mineralocorticoid hormone that is thought to be involved in the process of renal fibrosis independent from its actions to increase blood pressure by mediating salt retention.…”

ROCK (RhoA/Rho Kinase) in Cardiovascular–Renal Pathophysiology: A Review of New Advancements

“…The balance between RhoA/Rho kinase pathway and NO system plays a crucial role in the cardiovascular and renal dysfunction, providing induction/decrease of oxidative stress and inhibition/activation of PI3K/Akt [40]. The production of superoxide anion (O 2 − ) from NO results in endothelial dysfunction and accumulation of cytosolic Ca 2+ that could affect myocardial relaxation and contractility [41].…”

The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease

“…The highly complex renal pathways involved in the induction of oxidative stress entail the activation of the renin-angiotensin system (RAS). This latter in fact, by regulating several components of the cardiovascular-renal system, influences also pathophysiological responses through hypertension, rapid progression of atherosclerosis, and vascular remodeling [3]. Particularly in kidney disease, the excessive activation of the RAS and the excessive presence of oxidative stress participate together as playing a game in the progression of structural changes in the vessels and in the heart.…”