Multigene kinase network, kidney transport, and salt in essential hypertension.
Evidence is mounting that a multi-gene kinase network is central to the regulation of renal Na(+) and K(+) excretion and that aberrant signaling through the pathway can result in renal sodium retention and hypertension (HTN). The kinase network minimally includes the Ste20-related proline-alanine-rich kinase (SPAK), the with-no-lysine kinases (WNKs), WNK4 and WNK1, and their effectors, the thiazide-sensitive NaCl cotransporter and the potassium secretory channel, ROMK. Available evidence indicates that the kinase network normally functions as a switch to change the mineralocorticoid hormone response of the kidney to either conserve sodium or excrete potassium, depending on whether aldosterone is induced by a change in dietary sodium or potassium. Recently, common genetic variants in the SPAK gene have been identified as HTN susceptibility factors in the general population, suggesting that altered WNK-SPAK signaling plays an important role in essential HTN. Here, we highlight recent breakthroughs in this emerging field and discuss areas of consensus and uncertainty.
Welling
Paul A
PA
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Chang
Yen-Pei C
YP
Delpire
Eric
E
Wade
James B
JB
D001692:Biological Transport; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000378:metabolism*; D010770:Phosphotransferases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000378:metabolism
D017673:Sodium Chloride, Dietary; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human