These findings are believed to be the first confirmation in humans that Viagra has a direct effect on the heart. In earlier research, Kass and his team observed a similar effect in mice; Sildenafil blocked the short-term effects of hormonal stress in the heart.

Related studies by the group show that sildenafil also prevents and reverses the long-term effects of chronic high blood pressure on the heart.

Sildenafil reversed the negative effects on heart muscle weakened by heart failure and enlargement -- a condition called hypertrophy -- in mouse experiments Kass and his team carried out earlier this year. They reported their results in the journal Nature Medicine .

"But we had no firm evidence as to whether or how this therapy might work in the human heart," says Kass. "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 Johns Hopkins 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 assigned randomly to a group that was treated with sildenafil (100 milligrams taken orally) or to a group given a sugar pill placebo. All participants then were given the second dobutamine injection to see what effects sildenafil or placebo had on the heart.

"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," notes Kass.

After the first injection of dobutamine, the force of heart contraction increased by 150 percent in both groups. 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.

"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), Kass explains. This enzyme is involved in the breakdown of a key molecule, cyclic GMP, which helps control stresses and limit overgrowth in the heart.

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