Emory Report

June 22, 1998

 Volume 50, No. 34

Sodium retention may lead to high blood pressure, cancer

Sodium transport, the kidney function that regulates the level of salt in the kidney and bloodstream and, ultimately, blood pressure, may be intimately related to some of the same genes that have been implicated in the unchecked cellular growth of cancer. Douglas Eaton, associate professor of physiology and pediatrics and director of the Center for Cell and Molecular Signaling, presented the findings recently at the Experimental Biology '98 Meeting in San Francisco.

Eaton and his colleagues examined genetic, hormonal and pharmacologic changes that affect the sodium channels, special protein molecules found in a type of kidney cell. Sodium channels act as a gatekeeper by retaining salt in the kidney or by allowing salt to enter the bloodstream in response to changes in blood pressure. Small alterations in these molecules cause them to retain too much salt, which can lead to high blood pressure. About 30 percent of people who have hypertension, or high blood pressure, are reacting to the buildup of too much sodium.

"If the sodium channels are too active," Eaton said, "then people retain sodium, causing water build-up and an abnormal rise in blood pressure."

Hypertension affects an estimated 62 million Americans and is an underlying cause of heart attacks, heart failure and strokes, as well as kidney failure. Some people have a specific genetic abnormality that affects the sodium channels, but in other people there is nothing obviously wrong.

"In this other group of people, the sodium channels are switched on or off incorrectly by another molecule," said Eaton.

The steroid hormone aldosterone regulates how much sodium is released or retained by the sodium channels. In turn, steroid hormones like aldosterone work by switching on and off other proteins. Eaton and his colleagues have found that one of those other proteins is the cancer gene (oncogene) p21 ras, which has been implicated in a variety of cancers.

"It was a complete surprise to us that an oncogene implicated in cancer development would also be used to turn on and off the function of a sodium transport cell," noted Eaton. In addition, he and his colleagues found that another cancer gene, src kinase, is also responsible for regulating the actions of sodium channels in some individuals.

Learning how the kidney cells communicate and how they are regulated to maintain the complex balance of salt and fluid will help researchers better understand how kidney diseases begin and how hypertension might be controlled more successfully.

-Holly Korschun

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