Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension.
Potassium deficiency is associated with an increased prevalence of hypertension. Increasing potassium intake lowers blood pressure via an unknown mechanism. WNK (with no lysine) kinases are a novel family of large serine/threonine protein kinases. A large deletion from the first intron of the WNK1 gene results in increased levels of expression of WNK1 and causes Gordon's syndrome, of which hypertension and hyperkalemia are features. WNK1 activates the Na(+)/Cl(-) cotransporter NCC and the epithelial Na(+) channel ENaC, and inhibits the renal K(+) channel ROMK. Enhanced Na(+) reabsorption and inhibition of K(+) secretion resulting from increased WNK1 expression probably contribute to hypertension and hyperkalemia in Gordon's syndrome. Here, we review the role of dietary K(+) deficiency in the pathogenesis of salt-sensitive hypertension and summarize recent findings indicating that WNK1 might mediate renal Na(+) retention and hypertension in K(+) deficiency.
Huang
Chou-Long
CL
Division of Nephrology, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856, USA. chou-long.huang@utsouthwestern.edu
Kuo
Elizabeth
E
D006801:Humans; D006977:Hypertension, Renal / Q000453:epidemiology / Q000378:metabolism*; D007008:Hypokalemia / Q000453:epidemiology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007684:Kidney Tubules / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D011188:Potassium / Q000378:metabolism; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000493:pharmacokinetics*; D000076204:WNK Lysine-Deficient Protein Kinase 1
D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D017673:Sodium Chloride, Dietary; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; D011188:Potassium