Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

OHSU researchers identify master switch that regulates blood pressure

05.11.2007
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 today (NOV. 1) 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.”

Harry Lenhart | EurekAlert!
Further information:
http://www.ohsu.edu
http://www.ohsu.edu/nephrology/
http://www.the-jci.org/article.php?id=32033

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Camera on NASA's Lunar Orbiter survived 2014 meteoroid hit

29.05.2017 | Physics and Astronomy

Strathclyde-led research develops world's highest gain high-power laser amplifier

29.05.2017 | Physics and Astronomy

A 3-D look at the 2015 El Niño

29.05.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>