Aldosterone Receptors and Their Renal Effects: Molecular Biology and Gene Regulation

Abstract

Steroid hormones bind to and activate intracellular receptors that act as transcription factors that induce the synthesis of specific proteins within the target cells. Aldosterone binds to high-affinity cytoplasmic and nuclear receptors in the kidney and other mineralocorticoid target organs, inducing the synthesis of proteins that mediate the best understood effects of aldosterone. Aldosterone injected intra-arterially or into the renal artery resulted in a decrease in sodium and increased potassium excretion with a delay of 5–30 minutes, with no consistent effect in glomerular filtration rate. Acute subcutaneous administration of aldosterone increases sodium efflux from rat-tail artery smooth muscle due to a specific action on mineralocorticoid receptor (MR). Aldosterone has two types of action on sodium transport: a very rapid increase of passive sodium efflux, insensitive to actinomycin D (inhibitor of transcription), and a delayed stimulation of ouabain-dependent sodium efflux and an ouabain-independent sodium efflux that are completely blocked by actinomycin D. Both the early and late effects were blocked by the spirolactone. These studies indicated that aldosterone had an early, nongenomic effect on sodium transport that was mediated by the MR and a late or classic genomic effect mediated by the MR.