Study Could Aid Development of Improved Blood Pressure Drugs

Findings from a new study could aid in the development of safer and more effective blood pressure drugs, according to Loyola University Health System researchers.

The results also could help researchers predict whether drugs intended for other conditions, such as Alzheimer’s disease and epilepsy, would have either the detrimental effect of increasing blood pressure or the beneficial effect of lowering blood pressure. The findings could apply to drugs that are under development or already on the market.

“The implications are broad,” said Kenneth Byron, associate professor in the department of pharmacology at Loyola University Chicago Stritch School of Medicine.

Byron is senior author of the study, published in the May issue of the Journal of Pharmacology and Experimental Therapeutics.

About one in three adults in the United States—73 million people—have High Blood Pressure. The condition can lead to heart disease, heart failure, stroke, kidney failure and other problems. In 2004, High Blood Pressure killed nearly 55,000 people in the U.S., a 56 percent increase from 1994, according to the American Heart Association.

There’s a need for more blood pressure medications, said Dr. Ivan Pacold, associate professor of medicine in the department of cardiology at Stritch. Some patients need several drugs to control their blood pressure, but might experience side effects such as kidney problems or chemical imbalances from one of the drugs, Pacold said.

At Loyola, Byron’s research team discovered that certain classes of drugs can have dramatic effects on blood flow and blood pressure. The mechanism for this effect involves “potassium channels”—cellular gateways where potassium flows out of a cell. This flux of potassium is essential for normal heart, digestive and muscular functions.

Researchers investigated a particular type of potassium channel in laboratory studies. They found that when a given drug blocks these potassium channels in the muscle cells of artery walls, blood pressure increases. Conversely, if a drug opens up potassium channels, blood pressure goes down.

“By observing the impact of a drug on these particular potassium channels, you can predict its impact on blood pressure,” Byron said. “Here at Loyola, we have worked out how to accurately measure these channels in the muscle cells from the artery wall. So far we are the only lab in the world that has succeeded in doing this.”

For example, an experimental drug for the treatment of epilepsy likely would lower blood pressure because it opens the potassium channel, Byron said. But an experimental Alzheimer’s disease drug, which blocks the potassium channel, probably would have the opposite effect of increasing blood pressure.

“We still are in the early stages of this work,” Byron said. “But with continued funding, we believe our findings could lead to major benefits in the treatment of hypertension or stroke.”

Co-authors of the study, all from Loyola, are Alexander Mackie, Lioubov Brueggemann, Kyle Henderson, Aaron Shiels, Leanne Cribbs and Karie Scrogin.

The study was supported with funding from the National Heart Lung and Blood Institute and the American Heart Association.

Source: Loyola University Health System