Glucocorticoids and renal sodium transport: implications for hypertension and salt-sensitivity

Robert W Hunter, Jess Ivy, Matthew A Bailey

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

The clinical manifestations of glucocorticoid excess include central obesity, hyperglycaemia, dyslipidaemia, electrolyte abnormalities and hypertension. A century on from Cushing's original case study, these cardinal features are prevalent in industrialised nations. Hypertension is the major modifiable risk factor for cardiovascular and renal disease and reflects underlying abnormalities of sodium homeostasis. Aldosterone is a master regulator of renal sodium transport but here we argue that glucocorticoids are also influential, particularly during moderate excess. The hypothalamic-pituitary-adrenal axis can affect renal sodium homeostasis on multiple levels, systemically by increasing mineralocorticoid synthesis and locally by actions on both the mineralocorticoid and glucocorticoid receptors, both of which are expressed in the kidney. The kidney also expresses both of the 11β-hydroxysteroid dehydrogenase enzymes. The intrarenal generation of active glucocorticoid by 11βHSD1 stimulates sodium reabsorption; failure to down-regulate the enzyme during adaption to high dietary salt causes salt-sensitive hypertension. The deactivation of glucocorticoid by 11βHSD2 underpins the regulatory dominance for sodium transport of mineralocorticoids and defines the "aldosterone-sensitive distal nephron". In summary, glucocorticoids can stimulate renal transport processes conventionally attributed to the renin-angiotensin-aldosterone system. Importantly, sodium and volume homeostasis do not exert a negative feedback on the hypothalamic-pituitary-adrenal axis. These actions are therefore clinically relevant and may contribute to the pathogenesis of hypertension in conditions associated with elevated glucocorticoid levels, such as the metabolic syndrome or chronic stress.
Original languageEnglish
Pages (from-to)1731-1744
JournalJournal of Physiology
Volume592
DOIs
Publication statusPublished - 17 Feb 2014

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