ATHENS, Ohio -- Three of the most widely prescribed drugs used to treat hypertension may do more than reduce blood pressure in people who take them. They also may help prevent a type of cell damage caused by too much oxygen in the blood, according to a new study by researchers at Ohio University.
"Antihypertensive drugs are the second most frequently prescribed drug in the United States. Clearly, if you have a significant portion of the population taking these drugs, it's necessary to study the drugs' effects -- positive and negative -- on the body," said Peter Johnson, professor of chemistry and biomedical sciences at Ohio University and co-author of the study.
Studies of the drugs -- captopril, hydralazine and terazosin -- found that, in some cases, the medications enhanced a protection mechanism the body employs when cells come under oxidative stress, a process caused by the production of free radicals released during the metabolism of oxygen. Free radicals are chemical byproducts of normal aerobic activities and can damage a cell's membrane, proteins and DNA. 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, Johnson said.
For the studies, the researchers gave high doses of the drugs to two groups of rats -- one group with high blood pressure and the other with normal blood pressure levels.
In the majority of the animal studies, each of the drugs helped to stimulate the expression of these antioxidant enzymes, which enables the body to protect its cells from oxidative damage. But in a few cases, the drugs produce the opposite effect, inhibiting the body's production of these protective enzymes.
"Each of the drugs we studied seems to have an effect on antioxidant enzyme level expression, but the effects are different from drug to drug," Johnson said. "More surprisingly, the effects were different in different groups of animals," which could mean that a drug that causes no problem in one animal may present problems in another.
More than 50 million Americans have hypertension, or high blood pressure, and are treated with dozens of drugs. Most antihypertension medications have different, primarily non-threatening, side effects that range from water retention to skin irritation. But Johnson's studies suggest some of these drugs also affect cells in a way not studied before.
"We weren't really surprised to find that captopril caused a change in antioxidant enzyme expression," Johnson said. "The drug is now being used by some physicians in heart attack recovery therapy because people suspect it may be an antioxidant itself."
Researchers were surprised, however, to find that the other drugs in the study -- hydralazine and terazosin -- also had an impact on enzyme expression. In some cases, the drugs produced an increase in enzyme activity, which heightens the body's response to oxidative stress. But in others, it inhibited that protective process.
"This is the first time that these two commonly prescribed drugs have been shown to affect antioxidant enzyme activities," Johnson said. "It's something physicians need to be mindful of, because if something in the body already is out of balance because of hypertension, these drugs could make things even more out of balance."
The work was published in a recent issue of the journal Biochemical Pharmacology and was co-authored by Karen S. Cabell, a medical student in the College of Osteopathic Medicine and Lin Ma, a graduate student in chemistry, both at Ohio University.
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