title: The role of aldosterone in renal sodium transport.
abstract: Aldosterone is the body's major hormone involved in volume homeostasis because of its effects on sodium reabsorption in the distal nephron. Our comprehension of the signaling pathways that this mineralocorticoid unleashes has been enhanced through the convergence of bedside physiologic observations with advances in medical genetics and molecular biology. This overview updates our current understanding of the aldosterone-initiated pathways throughout the distal nephron to promote sodium retention. Three essential features of the pathways are explored: how the mineralocorticoid gains specificity and targets gene transcription in distal tubular cells; how the key endpoints of aldosterone action in these cells-the epithelial sodium channel, the thiazide-sensitive sodium chloride cotransporter, and Na,K,ATPase-are regulated; and how 3 kinases, directly or indirectly, are activated by aldosterone and serve as critical intermediaries in regulating the sodium transporters. Remarkably, perturbations in many genes integral to aldosterone-induced pathways result in blood-pressure abnormalities. The familial disorders of hypertension and hypotension that follow from these mutated genes are presented with their molecular and physiologic consequences. The clustering of so many genetic disorders within the aldosterone-sensitive distal nephron supports the hypothesis that renal sodium regulation plays a pivotal role in long-term blood-pressure control. Identifying and characterizing other components of the pathways that modulate these sodium transporters represent the core challenges in this scientific field. It is posited that meeting these challenges will help elucidate the pathogenesis of human hypertension and provide new therapeutic options for its treatment.
authors.affiliation: Division of Nephrology, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. rozansky@ohsu.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Rozansky
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009399:Nephrons / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D000450:Aldosterone; D012964:Sodium