Aldosterone and Blood Pressure Regulation

Abstract

T he purpose of this brief review is to highlight 3 recent conceptual advances in the ongoing exploration of the biology of aldosterone and how disorders of aldosterone metabolism and action lead to hypertension. Notably, important contributions to the advancement of our understanding in all 3 areas were published within the pages of Hypertension.For >60 years, the link between aldosterone and hypertension has remained a key focus of research. The focus on this hormone and how it regulates blood pressure (BP) date back to a period of time when its putative existence, separate from that of glucocorticoids, was only speculated. The research intensity in the field accelerated with the initial report of the isolation of aldosterone (originally named electrocortin) 1 in the early 1950s and the identification of its critical role in mediating the effects of activation of the renin-angiotensin system. Since then we have seen a continuously accelerating trajectory of research intensity.Advances in our understanding of the biology and pathobiology of aldosterone have been critical to our understanding of the mechanisms of hypertension and its management. A PubMed search of this connection between hypertension and aldosterone demonstrates its ongoing importance. For listings through September 2013, the search strategy (hypertension OR blood pressure AND aldosterone OR mineralocorticoid) returned 18 514 references dating from 1948. Notably >10% of those reports (2031) have been published during the past 3 years, a testament to the ongoing importance of this area of research.From this quantitatively and qualitatively impressive body of scholarship, I have identified 3 themes that I believe represent significant advances in our understanding of the link aldosterone and hypertension taken from studies published during the past 3 years in Hypertension and in other high impact journals. They are the following:1. Emerging concepts related to the mechanisms by which aldosterone mediates its cardiovascular effects, especially those acting through rapid pathways 2. New insights into the mechanisms of aldosterone secretion, which impact on hyperaldosteronism syndromes 3. Advances in the management of resistant hypertension as they relate to aldosterone inhibition. The Cardiovascular Actions of Aldosterone: Unappreciated Actions, Unappreciated Mechanisms of EffectUntil recently, the role of aldosterone in cardiovascular regulation and its mechanism of action in BP control were thought to be restricted to its renal effects. Aldosterone was widely seen as a hormone whose actions were predominantly related to renal sodium regulation and whose main mechanism of action was thought to be via regulation of transcription. However, during the past decade, important extrarenal, cardiovascular actions of aldosterone have been reported, viz. on vascular smooth muscle contractility, cardiac fibrosis, cardiac inotropy, and on growthand death-regulatory mechanisms. 2 Furthermore, beyond its direct transcriptional regulatory effects, aldosterone has...

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