Study Describes Molecules That Control Blood Pressure

The finding involving proteins could lead to new treatments, researchers say

By Ed Edelson
HealthDay Reporter

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FRIDAY, Nov. 2 (HealthDay News) -- Researchers are reporting a newly discovered molecular mechanism that makes blood pressure go up or down -- knowledge that could lead to new treatments for the hypertension that affects at least 50 million Americans.

A report published Nov. 1 in the Journal of Clinical Investigation is the latest in a series of studies on molecules called WNK kinases, which are proteins that help regulate blood pressure, said study co-author Dr. David H. Ellison, a professor of medicine at the Oregon Health & Science University.

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"It has been known that these kinases are important for regulating blood pressure, because mutations of them cause hypertension," Ellison said. "This report adds two things that were not previously known."

One new finding was that one kinase, WNK3, plays a key role in regulating NCC, a protein that normally keeps salt in the body. Salt content helps govern blood pressure; more salt means higher pressure.

Another finding was that WNK3 does not act alone but in conjunction with two other kinases, WNK1 and WNK4. The interaction of WNK3 and WNK4 is important, Ellison said, because it helps explain why fruits and vegetables, which are rich in potassium, help keep blood pressure low.

Start with WNK4. If extra copies of a gene for the normal version of the kinase are put into a laboratory animal, its blood pressure goes down. If extra copies of a mutated version of WNK4, differing in only one of the amino acid units making up the protein, are added, its blood pressure goes up, Ellison said.

"It has been shown that the mutant of WNK4 causes disruption of the normal form of its metabolic pathway," he said. "There is continuing salt resorption caused by an interaction with the normal form, which turns off the normal form."

Potassium keeps blood pressure down by stimulating production of WNK4, Ellison said. The extra WNK4 reduces the activity of WNK3. The entire complex of three WNK kinases also acts as a unit, modifying the activity of the NCC protein.

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