ATHENS, Ohio -- New studies of a drug taken by millions of hypertension sufferers suggest it may have a positive side effect that could lead to healthier cells, according to researchers at Ohio University.
"Hydralazine is a very commonly used drug, and it's been used for years," said Peter Johnson, professor of biomedical sciences and chemistry at Ohio University and co-author of the study. "It's sort of reassuring that it doesn't have any negative effects on cells and that it can have positive implications."
Johnson's studies suggest that hydralazine, taken by millions of people with high blood pressure since the early 1950s, improves cell health by decreasing the number of free radicals -- chemical byproducts of normal aerobic activities that can damage a cell's membrane, proteins and DNA. These new studies contradict previous research performed in purely chemical systems that suggested hydralazine was a free-radical generator and potentially harmful to cells.
A healthy body reacts to free radicals by producing antioxidant enzymes, which neutralize the free radicals before they can harm cells. When the production of free radicals is elevated, as is the case with hypertensive patients, a cell's ability to release these protective enzymes is affected.
Hydralazine and captopril, another popular antihypertension drug, are used to lower high blood pressure by relaxing the blood vessels. Only in the past several years have researchers discovered these drugs' effects on the production of free radicals in cells.
Some drugs, such as hydralazine, were thought to increase free radicals. Others, such as captopril, are antioxidants, which researchers believed made them natural free-radical inhibitors. But Johnson's latest research, which looked at both hydralazine and captopril, suggests captopril doesn't have an immediate antioxidant effect in cells.
"Captopril did not have the kind of positive effect on the cells that we found with hydralazine. It really had no effect," Johnson said. "That was another surprise."
Johnson attributes the contradictory findings to his research method. In the past, researchers have studied the effects of these drugs in either live animals or in chemical systems in test tubes. But researchers at Ohio University studied the drugs' reactions in isolated cells from the brains and immune systems of rats.
"By studying cells, you can study the acute effect of the drug during a period of hours, and you can do very sophisticated measurements," Johnson said.
In an earlier study, Johnson looked at the effects of these two drugs and a third drug, terazosin, on live rats during a 12-week period. He found that in most cases, the medications stimulated the antioxidant enzymes that neutralize free radicals. But in a few cases, the drugs produced the opposite effect, inhibiting the body's production of these protective enzymes.
About 30 percent of U.S. adults suffer from high blood pressure and are treated with dozens of different drugs. Most antihypertension medications have a variety of mostly nonthreatening side effects that range from water retention to skin irritation.
Johnson's work was published in a recent issue of the journal Free Radical Research and was co-authored by Yanzhang Wei, a former senior scientist in the Edison Biotechnology Institute; Matthew Huentelman and Craig Peters, 1998 graduates in chemistry from Ohio University; and Alexander Boldyrev, former visiting professor of chemistry from Moscow State University. Johnson is a professor in the College of Osteopathic Medicine and holds a joint appointment in the College of Arts and Sciences.
The research was supported in part by the Russian Foundation for Fundamental Research and through a Putnam professorship awarded to Boldyrev for his stay at Ohio University.
Contact: Peter Johnson, (740) 593-1744; pjohnson1@ohio.edu
Written by Melissa Rake, (740) 593-1891; rake@ohio.edu
Journal
Free Radical Research