Newly Discovered "Master Switch” Regulates Blood Pressure

A new study has identified the mechanism by which a protein complex in the kidney operates as a master switch that regulates blood pressure, a finding that has broad implications for the treatment of more common forms of hypertension.

Researchers at the Oregon Health & Science University (OHSU, Portland, USA) studied a rare disease called familial hyperkalemic hypertension (FHHt), in a search for clues to how blood pressure is regulated in the more common form of high blood pressure, known as essential hypertension. The researchers focused on the complex interactions between the with-no-Lysine Kinase-1 (WNK1), WNK3, and WNK4 kinases in regulating the thiazide-sensitive Na-Cl cotransporter (NCC), a salt transporter protein that normally keeps salt in the body. The researchers found that the WNKs form a protein-signaling complex, and that all three WNKs talk to each other and act as a rheostat-controlled amplifier that modulates the activity of NCC in response to physiological needs. FHHt, consequently, is caused by a glitch in communications between the different WNKs regulating the NCC. The study was published in the November 2007 issue of the Journal of Clinical Investigation.

"We think the answer is the WNK kinases, which switch aldosterone from a sodium chloride -retaining hormone to a potassium-wasting hormone,” said lead author David H. Ellison, M.D. "When you inherit a mutation in one of the WNK kinases the switch gets turned in the wrong direction. The switching mechanism explains for the first time why eating a high potassium diet lowers blood pressure. High potassium not only stimulates aldosterone secretion but also modulates WNK kinase activity; together aldosterone and certain WNK kinases cause the kidney to rid itself of potassium rather than reabsorbing salt.”

Aldosterone is a steroid hormone of the mineralocorticoid family produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood.


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