Mineralocorticoid Receptor Antagonists in Essential and Resistant Hypertension

Abstract

Background: Mineralocorticoid receptor antagonists are a second-line class of antihypertensive drugs, which have been accounted for as the optimal add-on therapy in the triple algorithm for the management of resistant hypertension. Objectives: To assess the effects of mineralocorticoid receptor antagonists in the treatment of patients with essential hypertension and resistant hypertension. Method: We conducted a meticulous review of the literature and comprehensive identification of the clinical trials assessing the efficacy of mineralocorticoid receptor antagonists in individuals with primary and resistant hypertension. Results: MRAs have been thoroughly tested in several clinical studies in relevance to blood pressure lowering effects, over the last six decades. Accumulating data observed that MRAs resulted in a significant reduction in blood pressure level in patients with resistant hypertension. In addition, spironolactone was found to beneficially affect the management of resistant hypertension. Conclusion: Mineralocorticoid receptor antagonists exert a significant antihypertensive effect. Future welldesigned randomized controlled studies are greatly needed to address crucial clinical aspects in the field.

Novel antihypertensive action of rutin is mediated via inhibition of angiotensin converting enzyme/mineralocorticoid receptor/angiotensin 2 type 1 receptor (ATR1) signaling pathways in uninephrectomized hypertensive rats

“…Together, mineralocorticoid receptor antagonists have opened a novel therapeutic window for the management of patients with secondary/ resistant hypertension (Faulkner & Belin de Chantemèle, 2019;Imprialos et al, 2018;Sato, 2019).…”

“…Hence, patients suffering from primary aldosteronism have an increased propensity to develop cardiovascular disease conditions and target organ damage (Stavropoulos et al., 2018). Together, mineralocorticoid receptor antagonists have opened a novel therapeutic window for the management of patients with secondary/ resistant hypertension (Faulkner & Belin de Chantemèle, 2019; Imprialos et al., 2018; Sato, 2019).…”

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H2S‐Nrf2 signaling

“…Mineralocorticoid receptor antagonists are potassium‐sparing diuretics, and these are clinically employed in the management of congestive heart failure [3]. However, studies have shown their expanding spectrum in a number of diseases including diabetic nephropathy [5], treatment‐resistant hypertension [6]. There have been studies showing that activation of mineralocorticoid receptors may be associated with impairment in memory [16], and blockade of these receptors may be beneficial in memory [17].…”

“…In clinics, these are predominantly used for the management of congestive heart failure and these have been reported to reduce cardiac remodeling and mortality rate in these patients [3]. Studies have shown their potential in modifying the pathogenesis of diseases including diabetic cardiomyopathy [4], diabetic nephropathy [5], treatment‐resistant hypertension [6], inflammasome formation [7], vascular dysfunction [8], and muscular dystrophy [9].…”

Top Ten Breakthroughs in Clinical Hypertension Research in 2022

“…Aldosterone exacerbates hypertension by promoting sodium reabsorption in distal nephrons by increasing the number and opening frequency of epithelium sodium channels, thereby leading to volume expansion. Additionally, aldosterone damages various target organs, including vessels, kidneys, and the heart, via multiple mechanisms, such as upregulation of connective tissue growth factor and subsequent fibrosis; production of proinflammatory molecules contributing to organ and extracellular matrix remodeling; oxidative stress; and stimulation of cell migration, proliferation, and apoptosis [28]. Moreover, target organ damage may worsen hypertension.…”