The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

Abstract

A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and “non-classical” variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

Conceptualization of Heterogeneity of Chronic Diseases and Atherosclerosis as a Pathway to Precision Medicine: Endophenotype, Endotype, and Residual Cardiovascular Risk

“…A number of researchers have identified various endotypes of hypertension: low-renin hypertension, salt-and-stress-sensitive hypertension, hypertension associated with obesity, etc. [27][28][29].…”

The Research Progress of Monogenic Inherited Hypertension

“…It is notable that both glycyrrhizic acid and grapefruit juice are HSD11B2 inhibitors and an excessive intake can induce clinical symptoms and laboratory findings of AME syndrome [29]. Baudrand and Vaidya conceived that lower cortisone levels (in combination with higher F/E ratio) were strongly associated with higher MR activity (lower renin activity and higher urinary potassium excretion) in patients suspected to have mild or non-classical AME [30].…”

Vascular Remodeling in Different Activity of Renin-Angiotenzin-Aldosterone System in Patients with Comorbidity of Arterial Hypertension and Obesity

“…терону, які беруть участь у блокаді ендотеліальної синтази оксиду азоту (NO) і знижують спорідненість ендотеліоцитів до NO [12][13][14].…”

“…Незважаючи на відомий факт про те, що активація РААС призводить до прогресування судинного ремоделювання, недостатньо вивченим залишається оцінювання її впливу при різній активності компонентів РААС, що відрізняє низькоренінову і високоренінову АГ (НРАГ і ВРАГ відповідно) [10][11][12][13][14].…”