Aldosterone: Role in the Cardiometabolic Syndrome and Resistant Hypertension

Aldosterone is synthesized in the zona glomerulosa of the adrenal gland in response to angiotensin II (Ang II), adrenocorticotropin (ACTH), potassium, and lipid soluble factor(s) produced in fat tissue ()., The classical genomic pathway of aldosterone action involves binding to cytosolic MRs and subsequent translocation to the nucleus, gene transcription, and translation of effector proteins involved in regulating sodium and potassium balance across renal tubular epithelial cells., Aldosterone also exerts rapid, non-genomic effects that mediate maladaptive tissue remodeling throughout the cardiovascular and central nervous system, further perpetuating the CMS, insulin resistance, and the hypertensive state. The non-genomic pathways of aldosterone are independent of renal tubular reabsorption of sodium and volume expansion and utilize rapid activation of the tyrosine kinase signaling and subsequent downstream activation of extracellular receptor kinase (ERK1/2), Rho kinase, and protein kinase (PKC) in association with increased cytosolic calcium and generation of reactive oxygen species (ROS).,– The consequences of activating these pathways are increased NADPH oxidase activation/ROS generation, mitochondrial electron transport uncoupling, and downstream activation of redox-sensitive serine kinases (–).,,, As MRs are expressed in numerous tissues, elevated circulating aldosterone levels signaling via nongenomic as well as genomic mechanisms result in a number of maladaptive tissuespecific effects ().

Publication

Aldosterone: Role in the Cardiometabolic Syndrome and Resistant Hypertension. () Adam Whaley-Connell, et al. Prog Cardiovasc Dis. ;52(5):401-409. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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