Viagra blunts effects of stress on the human heart

October 24, 2005

Sildenafil citrate (Viagra), a drug used to treat erectile dysfunction (ED) 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 heart beat 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, M.D., a professor at The Johns Hopkins University School of Medicine and its Heart Institute.

"Sildenafil effectively puts a 'brake' on chemical stimulation of the heart," says Kass.

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 adds, 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, adrenaline-like 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," adds Kass.

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," says Kass. "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 adds.

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 (PDE5A), the researcher says. 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.
-end-
Funding for this study was provided by the National Institutes of Health (NIH), 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.

The study, conducted solely at Hopkins, was led by cardiologist Barry Borlaug, M.D. Other researchers involved in this study were Vojtech Melenovsky M.D., Ph.D.; Tricia Marhin, R.N., B.S.N.; and Patricia Fitzgerald, R.N., B.S.N. Kass is also the Abraham and Virginia Weiss Professor of Cardiology at Hopkins.

Johns Hopkins Medicine

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