Role of Sgk1 in salt and potassium homeostasis

V Vallon, P Wulff, DY Huang, J Loffing… - American Journal …, 2005 - journals.physiology.org
V Vallon, P Wulff, DY Huang, J Loffing, H Völkl, D Kuhl, F Lang
American Journal of Physiology-Regulatory, Integrative and …, 2005journals.physiology.org
Aldosterone plays a pivotal role in NaCl and K+ homeostasis by stimulation of Na+
reabsorption and K+ secretion in the aldosterone-sensitive distal nephron (ASDN). Recent
studies demonstrated that the serum-and glucocorticoid-regulated kinase 1 (Sgk1) is
induced by aldosterone in the ASDN and that polymorphisms of the kinase associate with
arterial blood pressure in normotensive subjects. This review discusses the role of Sgk1 in
NaCl and K+ homeostasis as evidenced by in vivo studies, including those in Sgk1-deficient …
Aldosterone plays a pivotal role in NaCl and K+ homeostasis by stimulation of Na+ reabsorption and K+ secretion in the aldosterone-sensitive distal nephron (ASDN). Recent studies demonstrated that the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by aldosterone in the ASDN and that polymorphisms of the kinase associate with arterial blood pressure in normotensive subjects. This review discusses the role of Sgk1 in NaCl and K+ homeostasis as evidenced by in vivo studies, including those in Sgk1-deficient mice. The studies indicate that Sgk1 is not absolutely required for Na+ reabsorption and K+ secretion in the ASDN. On a standard NaCl and K+ diet, modestly enhanced plasma aldosterone concentrations appear sufficient to establish a compensated phenotype in the absence of Sgk1. The kinase is necessary, however, for upregulation of transcellular Na+ reabsorption in the ASDN. This may involve Sgk1-mediated stimulation of basolateral Na+-K+-ATPase as well as retention of epithelial Na+ channel, ENaC, in the apical membrane. Such an upregulation is a prerequisite for adequate adaptation of 1) renal NaCl reabsorption during restricted dietary NaCl intake, as well as 2) K+ secretion in response to enhanced K+ intake. Thus gain-of-function mutations of Sgk1 are expected to result in renal NaCl retention and enhanced K+ secretion. Further studies are required to elucidate renal and nonrenal aldosterone-induced effects of Sgk1, the role of other Sgk1 activators, as well as the link of Sgk1 polymorphisms to arterial hypertension in humans.
American Physiological Society