Immune System Alterations by Aldosterone During Hypertension: From Clinical Observations to Genomic and Non-Genomic Mechanisms Leading to Vascular Damage

Abstract

Hypertension is traditionally considered a disease in which elevated blood pressure contributes to inflammation and activation of the immune system, leading to cardiovascular injury and end-organ damage. Here, we discuss the effects of aldosterone on the immune system and aldosterone's contribution to vascular pathogenesis. Studies in human have suggested a broader role for aldosterone, beyond elevating blood pressure. Recent clinical data support the notion that aldosterone can directly alter the function of the immune system and cause vascular-damaging inflammation. Clinical observations have been reproduced in experimental models of hypertension, further supporting the idea that an aberrant immune response contributes to the onset of hypertension. Such studies have shown that myeloid cells are required to induce the disease and IL-17-producing CD4(+) T cells may contribute to maintaining aldosterone-mediated hypertension. In addition, regulatory T cells diminish the inflammatory damage caused by aldosterone during hypertension. This is a very active area of research that could lead to new therapeutic targets for treating hypertension.

Urinary Exosomes and Their Cargo: Potential Biomarkers for Mineralocorticoid Arterial Hypertension?

“…The pathogenesis of AHT involves the renal, vascular, and endocrine systems ( 12 – 15 ), affecting mainly sodium-water reabsorption and arterial vasoconstriction. Pathological conditions, such as primary aldosteronism (PA), are responsible for up to 5–10% of patients diagnosed with AHT, and involve an increased production of aldosterone that leads to AHT, cardiovascular damage, heart diseases ( 16 – 18 ), and renal and immune alterations ( 19 – 23 ). Aldosterone is a mineralocorticoid hormone with non-genomic and genomic actions; the latter through the mineralocorticoid receptors (MR) can alter sodium transport in renal collecting ducts, increase water uptake, blood volume, and eventually raise blood pressure.…”

Hiperaldosteronismo primario y otras formas de hipertension arterial endocrina

“…También, estudios recientes han demostrado que la aldosterona puede afectar al sistema inmune modulando la actividad de células dendríticas que inducen la activación y polarización de linfocitos T a Linfocitos Th17 que producen interleukina 17, la cual se ha relacionado con enfermedades autoinmunes (Munoz-Durango et al 2013;Munoz-Durango et al 2015).…”

“…2008). *** El punto de corte superior para la razón F/E es variable para adultos y niños, valor que puede aumentar con la edad en sujetos normotensos (Campino et al 2013).…”

Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

“…Currently, the physiopathology of cardiovascular diseases, such atherosclerosis [ 63 ] and hypertension, are considered to be closely related with inflammatory processes [ 64 , 65 ]. As a result, inflammatory cells infiltrate the tissues producing proinflammatory cytokines and inducing the generation of oxidative stress, which leads to fibrosis and end-organ damage [ 18 ]. The Renin-Angiotensin-Aldosterone System (RAAS) has been closely related with the deleterious effect seen in patients with cardiovascular diseases, turning RAAS into an important axis that could be intervened to reduce disease [ 17 , 18 ].…”

“…In the context of the immune response, it has been consistently reported that aldosterone stimulation promotes proinflammatory responses in various tissues [ 17 , 18 ]. In human leucocytes, MR expression has been reported in CD34+ hematopoietic progenitor, also in peripheral blood T and B lymphocytes, monocytes, and neutrophils [ 19 ].…”