Aldosterone plays a major role in the regulation of
sodium and
potassium homeostasis and blood pressure. More recently,
aldosterone has emerged as a key
hormone mediating end organ damage. In extreme cases, dysregulated
aldosterone production leads to primary
aldosteronism (PA), the most common form of secondary
hypertension. However, even within the physiological range, high levels of
aldosterone are associated with an increased risk of developing
hypertension over time. PA represents the most common and curable form of
hypertension, with a prevalence that increases with the severity of
hypertension. Although genetic causes underlying
glucocorticoid-remediable aldosteronism, one of the three Mendelian forms of PA, were established some time ago, somatic and inherited mutations in the
potassium channel GIRK4 have only recently been implicated in the formation of
aldosterone-producing
adenoma (APA) and in
familial hyperaldosteronism type 3. Moreover, recent findings have shown somatic mutations in two additional genes, involved in maintaining intracellular ionic homeostasis and cell membrane potential, in a subset of APAs. This review summarizes our current knowledge on the genetic determinants that contribute to variations in plasma
aldosterone and
renin levels in the general population and the genetics of familial and sporadic PA. Various animal models that have significantly improved our understanding of the pathophysiology of excess
aldosterone production are also discussed. Finally, we outline the cardiovascular, renal, and metabolic consequences of
mineralocorticoid excess beyond blood pressure regulation.