Blood pressure effects of sodium transport along the distal nephron

• Published in: Kidney international Vol. 102; no. 6; pp. 1247 - 1258
• Main Authors: Castañeda-Bueno, María, Ellison, David H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2022
• Subjects: Aldosterone - metabolism; Animals; Blood Pressure; Humans; Hypertension; Mammals - metabolism; Nephrons - metabolism; potassium channels; renin angiotensin system; salt; Sodium - metabolism; renin angiotensin system; potassium channels; salt
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1016/j.kint.2022.09.009

The mammalian distal nephron is a target of highly effective antihypertensive drugs. Genetic variants that alter its transport activity are also inherited causes of high or low blood pressure, clearly establishing its central role in human blood pressure regulation. Much has been learned during the past 25 years about salt transport along this nephron segment, spurred by the cloning of major transport proteins and the discovery of disease-causing genetic variants. Recognition is increasing that substantial cellular and segmental heterogeneity is present along this segment, with electroneutral sodium transport dominating more proximal segments and electrogenic sodium transport dominating more distal segments. Coupled with recent insights into factors that modulate transport along these segments, we now understand one important mechanism by which dietary potassium intake influences sodium excretion and blood pressure. This finding has solved the aldosterone paradox, by demonstrating how aldosterone can be both kaliuretic, when plasma potassium is elevated, and anti-natriuretic, when extracellular fluid volume is low. However, what also has become clear is that aldosterone itself only stimulates a portion of the mineralocorticoid receptors along this segment, with the others being activated by glucocorticoid hormones instead. These recent insights provide an increasingly clear picture of how this short nephron segment contributes to blood pressure homeostasis and have important implications for hypertension prevention and treatment.