Hypertension Drug May Restore Cardiovascular Function In African Americans

Tadeusz Malinski, Marvin & Ann Dilley White Professor in the Department of Chemistry and Biochemistry, found that the drug, currently under review by the U.S. Food and Drug Administration, acts on the level of oxidants lining the cardiovascular system and can restore levels of nitric oxide and reduce oxidative stress. A deficiency in nitric oxide and high oxidative stress can cause a variety of health problems, including heart attacks, stroke and heart failure, as well as kidney failure and diabetes.

The study was published in a recent issue of Circulation, an American Heart Association Journal, and involved collaborators from Harvard Medical School and Elucida Research in Massachusetts.

In a healthy cardiovascular system, there is a fine balance between nitric oxide and oxidative stress. Nitric oxide controls blood flow and relaxes blood vessels, which lowers blood pressure. The nitric oxide is released by endothelial cells, a monolayer of cells lining blood vessels.

About a year ago, Malinski’s research team discovered that African Americans potentially have a better nitric oxide generating system than people of other ethnicities, the researcher reported. Due to a molecular deficiency, however, the system becomes self-destructive by also generating high concentrations of oxidative species that diminish the level of good nitric oxide and increase oxidative stress to the level observed in a diseased state. The prevalence of this problem can be blamed for the high mortality rate of African Americans between 43 and 64 years of age, which is five to six times higher than that of other ethnic groups, Malinski said.

That’s where nebivolol may come in. The drug is part of a new generation of beta-blockers, which are standard treatments for high blood pressure. The researchers studied multiple versions of these beta-blockers and found that, besides lowering blood pressure, nebivolol also restored the function of the nitric oxide system in the cell samples.

“It is very rare that we see a dual positive effect of a drug in medical treatments,” Malinski said.

In the recent study, scientists used nanosensors to test levels of nitric oxide, as well as molecules involved in the oxidative stress, in single cells from donors of various ethnic backgrounds. Using nanosensors 1,000 times smaller than a human hair, the researchers could take real-time measurements of nitric oxide levels before and after nebivolol was administered. This nanomedical approach allowed the research to progress much faster than it would have with traditional methods of measuring nitric oxide levels.

“The drug restores correct balance between good nitric oxide and damaging oxidative stress, and can in fact restore the vital function of endothelial tissue to a level similar in other ethnic groups,” Malinski said of his team’s findings. “Previous treatments only slowed progression of the damage, while nebivolol may actually be able to correct the problems.”

Malinski and other researchers are currently investigating possible uses of the drug to prevent damage to the cardiovascular system.

Co-authors were Adam Jacoby and Leszek Kalinowski of Ohio University, Preston Mason Professor of Harvard Medical School and Robert Jacob of Elucida Research in Massachusetts.

The study was funded by the Marvin and Ann Dilley White Endowment and the Biomimetic Nanoscience and Nanotechnology Initiative, which part of a larger $8 million NanoBioTechnology Initiative that is one of three of Ohio University’s major research priorities.