Scientists use corrective gene to block a protein in the kidneys that triggers high blood pressure

Apr 11 2006

Nearly one-third of American adults have high blood pressure, a major cause of heart attacks, strokes and kidney failure. But a new technique tested at the University of Florida could prove to be a long-term way to treat the disorder in humans, researchers say.

UF researchers kept blood pressure from worsening and nearly eliminated kidney damage in rats exposed to cold weather, which can constrict blood vessels and overload the kidneys with hormones, according to findings published online recently in the journal Gene Therapy.

Using a corrective gene, scientists were able to block a protein in the kidneys that triggers high blood pressure and kidney damage, said Zhongjie Sun, M.D., Ph.D., a UF assistant professor of medicine, physiology and functional genomics and the lead author of the study.

The protein, called a mineralocorticoid receptor, signals the body to absorb sodium and water into the bloodstream. This increases the amount of blood in the body, also increasing blood pressure. While some treatments already on the market block the MR protein, the medications don't target it specifically, interfering with other receptors and causing unwanted side effects, Sun said.

"This new technique can specifically and efficiently inhibit the protein and prevent the progression of hypertension," Sun said. "I'm very optimistic this gene complex will be used for human gene therapy to treat hypertension."

To block the protein, researchers used a technique called RNA interference. A harmless virus ferries fragments of RNA into the body, where they infiltrate cells and stop the protein. It's the first time scientists have used the approach to treat hypertension and kidney damage, he said.

The treatment kept blood pressure from escalating but did not lower it to normal levels, most likely because the researchers monitored the rats only for three weeks after they were treated. Blood pressure continued to rise in rats that did not receive the therapy.

The researchers plan to study what happens to the rats when they are observed for a longer period of time after therapy, which Sun suspects will give their blood pressure more time to drop. It would be unhealthy for blood pressure to drop rapidly, in rats or humans, Sun added.

While researchers expected the treatment to prevent hypertension, they were surprised to discover that it dramatically reduced damage to the kidneys as well, Sun said. It was already known that hypertension can lead to kidney dysfunction, particularly in the later stages of the disease, but these findings show that the MR protein may play more of a role in causing kidney damage than researchers previously understood.

"Increased expression of this protein may cause kidney damage, which has nothing to do with pressure-induced kidney damage," Sun said.

Nearly 65 million Americans have high blood pressure and more than 50,000 people die each year from it, according to the American Heart Association. Blood pressure, which is measured as the rate of pressure in the arteries when the heart forces blood into the vessels over the rate of the heart at rest, is considered high if it rises above a 140/90.

Cold weather can elevate blood pressure. Because of this, heart attacks and strokes are often more common in winter. To simulate cold-induced hypertension in adults, three groups of six rats were housed in a cooled chamber, kept at a steady 44 degrees Fahrenheit for five weeks.