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Viagra Blunts Effects of Stress on the Human Heart
October 31, 2005
Sildenafil citrate (Viagra), a drug used to treat
erectile dysfunction in millions of men, reduces the stimulatory
effects of hormonal stress on the heart by half, according to results
of a new study by researchers at Johns Hopkins. While sildenafil
is more widely known for helping genital blood vessels expand to
maintain an erection and, more recently, as a treatment for pulmonary
hypertension, it has been thought to have little direct effect on
the human heart. In the heart, sildenafil blunts the strengthened
heartbeat caused by chemically induced stress, thereby lessening
the excess amount of blood and force used to pump it to the body,
according to study senior author and cardiologist David Kass of
the Johns Hopkins School of Medicine and its Heart Institute. "Sildenafil
effectively puts a 'brake' on chemical stimulation of the heart,"
said Kass, the Abraham and Virginia Weiss Professor of Cardiology.
The researchers' findings, which appear in the journal Circulation
online Oct. 24, are believed to be the first confirmation in humans
that sildenafil has a direct effect on the heart. Previous research
by Kass and his team showed that sildenafil had such effects in
mice, blocking the short-term effects of hormonal stress in the
heart. Related studies by the group also showed that sildenafil
prevents and reverses the long-term effects in the heart from chronic
high blood pressure. Moreover, Kass said, the latest Hopkins results
confirm that sildenafil
helps control heart function only when the heart is under duress,
but has little impact under normal conditions.
Separate research from Kass and his team published earlier this
year in the journal Nature Medicine showed that, in mice, sildenafil
could reverse the negative effects on heart muscle weakened by heart
failure and enlargement, a condition called hypertrophy. "But
we had no firm evidence as to whether or how this therapy might
work in the human heart. Our latest research provides firm evidence
this drug does indeed have an important impact on the heart."
Thirty-five healthy men and women, with an average age of 30 and
no previous signs of coronary artery disease, participated in the
six-month study. Within a three-hour timeframe, each participant
received two separate injections of dobutamine (5 micrograms per
kilogram for five minutes), a synthetic adrenalinelike chemical
that increases heart rate and pumping strength. Between injections,
study participants were randomly assigned to a group that was treated
with sildenafil (100 milligrams taken orally) or to a group given
a sugar pill placebo.
All participants were then given the second dobutamine injection
to see what effects sildenafil or placebo had on the heart. Measurements
of heart function were made before and after each injection. This
included blood pressure readings, electrocardiograms and echocardiograms,
as well as blood samples to confirm relatively equal levels of sildenafil
and other enzymes. Results showed that each dobutamine injection
stimulated heart function, increasing heart rate and the force of
each heartbeat used to pump blood throughout the body. "This
stimulation is similar to the way the nervous system normally increases
heart function when triggered by emotional or exercise stress, or
in diseases such as heart failure," Kass said. After the first
injection of dobutamine, the force of heart contraction increased
by 150 percent in both groups. And in the placebo group, this increase
repeated itself after the second injection. However, in the group
treated with sildenafil, the increased heartbeat was slowed by 50
percent, resulting in a smaller increase in blood flow and blood
pressure generated by the heart in response to chemical stimulation.
Between injections, heart function was not altered in the sildenafil
group, demonstrating the absence of adverse side effects on the
resting human heart. "Knowing more about the effects
of sildenafil on heart function will allow for safer evaluation
of its use as a treatment for heart problems," Kass said."Until
now, it was widely thought that drugs like sildenafil had no effects
on the human heart and that its only purpose was vasodilation in
the penis and the lungs. "Our results set the stage for further
studies of sildenafil's immediate and long-term effects on the heart
and its ability to modify other neurohormonal and stress stimuli,
including adrenaline and hypertension," he said. While the
precise biological actions of sildenafil in the heart are not fully
understood, the drug is known to work by stopping the action of
an enzyme called phosphodiesterase 5, or PDE5A, the researcher said.
This enzyme is involved in the breakdown of a key molecule, cyclic
GMP, which helps control stresses and limit overgrowth in the heart.
PDE5A is also the biological pathway blocked in the penis by sildenafil
to prevent the relaxation of blood vessels and maintain erections.
Funding for this study was provided by the National Institutes of
Health, the Peter Belfer Laboratory Foundation and the Bernard Family
Foundation. The makers of the drug had no involvement in the design
or support of the research.
To read more, visit…
http://www.jhu.edu/~gazette/2005/31oct05/31viagra.html
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