ATHENS, Ohio — Nebivolol, a drug for treatment of high blood pressure already
available in Europe, may restore damaged cardiovascular functions in African
Americans, according to a recent laboratory study at Ohio University.
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
“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
Co-authors were Adam Jacoby and Leszek Kalinowski
of Ohio University, Preston Mason Professor of Harvard
Medical School and Robert Jacob of Elucida Research
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.
Tadeusz Malinski ,
Paula Hale ,
of Chemistry and Biochemistry
Nanoscience and NanoTechnology Group