Featured Research

from universities, journals, and other organizations

Master Switch That Regulates Blood Pressure Identified

Date:
November 2, 2007
Source:
Oregon Health & Science University
Summary:
Researchers studying a rare form of hypertension has identified the mechanism by which they believe 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.

A team of Oregon Health & Science University researchers studying a rare form of hypertension has identified the mechanism by which they believe 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.

The team led by David H. Ellison, M.D. -- whose findings are described in a paper being published in the Journal of Clinical Investigation -- likens the switch to a rheostat that modulates the balance of salt and potassium in the kidney, thereby raising or lowering blood pressure.

When the switch malfunctions, the group suggests, high blood pressure or hypertension occurs, as it does when certain mutations in the WNK kinase protein complex are present. Those genetic defects cause a disease called familial hyperkalemic hypertension (FHHt), also called pseudohypoaldosteronism type 2 or Gordon's syndrome. The OHSU group and others have focused on FHHt, which is rare, in a search for clues to how blood pressure is regulated in the more common form of high blood pressure, known as essential hypertension, often labeled the silent killer.

Hypertension affects at least 50 million Americans and untold millions around the world and is a major cause of heart attacks, strokes and kidney failure. The root cause is unknown in 95 percent of cases. If the study's conclusions are borne out in further research, they can lead to better targeted and more effective drugs for the disease, said Ellison, a professor of medicine in the OHSU School of Medicine and head of its Division of Nnephrology and Hypertension.

"It is not widely understood by the general public that hypertension is most often a kidney disease," said Ellison. "If we can figure out the ways the kidney adjusts salt excretion, we can devise methods to prevent hypertension, cure it or design better treatments for it. Our findings in this study get us a step closer, we think."

Ellison and his colleagues, Chao-Ling Yang, M.D., and Xiaoman Zhu, M.D., M.S., focused in the study on the complex interactions between the WNK1, WNK3 and WNK4 kinases in regulating NCC, a protein that normally keeps salt in the body. They explain for the first time that WNK 3 plays a key role in this process and that none of the WNK kinases act alone but function as a unit.

"These WNKs form a protein signaling complex," said Ellison. "All three WNKs talk to each other. Only when you understand how they work together and talk to each other can you understand the real biology of the disease. The complex acts as a rheostat-controlled amplifier that modulates the activity of NCC, the salt transporter gene, in response to physiological needs. The disease really is caused by a glitch in communications between the different WNKs regulating NCC."

Protein kinases constitute one of the largest human gene families and are key regulators of cell function. There are 518 of them -- referred to as the human kinome -- and they coordinate a wide variety of complex biological functions. The WNK kinases, which were discovered in 2000, have been a subject of intense interest among medical researchers since 2001 when a group at the Yale University School of Medicine found a link between this class of kinases and FHHt. Ellison and his group subsequently found that mutations in WNK1 and WNK4 cause this disease by modulating NCC activity.

The current OHSU study explains how aldosterone, a hormone produced in the adrenal gland, can have different effects on sodium and potassium balance at different times. The hormone sometimes increases salt absorption and at other times increases potassium excretion, but how it knows which role to play has been a mystery.

"We think the answer is the WNK kinases, which switch aldosterone from a sodium chloride (salt) -retaining hormone to a potassium-wasting hormone," said Ellison. "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."

The OHU study also breaks new ground in refining the explanation of how WNK mutations cause FHHt.

"We showed that the way the mutations cause the disease is with the participation of WNK3," said Ellison. "Unlike WNK4, which inhibits NCC, the salt cotransporter, WNK3 has a stimulative effect. If there's more WNK3, you'll have more salt reabsorption, and if there's more WNK4, you'll have less. What also happens is that WNK4 normally inhibits WNK3, but mutant WNK4 blocks this effect, thereby generating more active WNK3, increasing salt transport and causing the disease."

Journal article: The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex, Journal Of Clinical Investigation, November 1, 2007

Yang is a research assistant professor and Zhu is a research associate, both in the Division of Nephrology and& Hypertension, OHSU School of Medicine.

Funding for the Ellison team's research was provided by The National Institutes of Health.


Story Source:

The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length.


Cite This Page:

Oregon Health & Science University. "Master Switch That Regulates Blood Pressure Identified." ScienceDaily. ScienceDaily, 2 November 2007. <www.sciencedaily.com/releases/2007/11/071101193330.htm>.
Oregon Health & Science University. (2007, November 2). Master Switch That Regulates Blood Pressure Identified. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2007/11/071101193330.htm
Oregon Health & Science University. "Master Switch That Regulates Blood Pressure Identified." ScienceDaily. www.sciencedaily.com/releases/2007/11/071101193330.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
How to Master Motherhood With the Best Work/Life Balance

How to Master Motherhood With the Best Work/Life Balance

TheStreet (Apr. 22, 2014) In the U.S., there are more than 11 million couples trying to conceive at any given time. From helping celebrity moms like Bethanny Frankel to ordinary soon-to-be-moms, TV personality and parenting expert, Rosie Pope, gives you the inside scoop on mastering motherhood. London-born entrepreneur Pope is the creative force behind Rosie Pope Maternity and MomPrep. She explains why being an entrepreneur offers the best life balance for her and tips for all types of moms. Video provided by TheStreet
Powered by NewsLook.com
Catching More Than Fish: Ugandan Town Crippled by AIDS

Catching More Than Fish: Ugandan Town Crippled by AIDS

AFP (Apr. 22, 2014) The village of Kasensero on the shores of Lake Victoria was where HIV-AIDS was first discovered in Uganda. Its transient population of fishermen and sex workers means the nationwide programme to combat the virus has had little impact. Duration: 02:30 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins