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Viagra May Reverse Enlarged-Heart Damage
By Amanda Gardner
HealthDay Reporter
SUNDAY, Jan. 23 (HealthDayNews) --Viagra, the drug most often associated with restoring male sexual powers, may play an entirely different role in treating enlarged hearts.
In male mice, sildenafil citrate (the generic name for Viagra) successfully treated enlargement and thickening of the heart, not only stopping further growth of the heart muscle, but also actually reversing the growth and damage that had already taken place.
Trials in humans are slated to get underway later this year.
"If, indeed, what works in mice works in humans, this will become a standard part of care," said Dr. Richard Stein, a national spokesman for the American Heart Association. "This is very important."
"By treating mice with Viagra in doses that would be similar to what a person would get, we found that we could block hypertrophy [enlarging and thickening of the heart muscles] and could prevent progression to heart failure," said study co-author Dr. Hunter Champion, an assistant professor of medicine at Johns Hopkins University School of Medicine. "Heart failure is a huge problem in the United States. It is the No. 1 reason for hospitalization through Medicare."
The findings, which will be published in the February issue of Nature Medicine, represent a "clinical home run," as Stein put it.
They also represent a scientific breakthrough because they revealed mechanisms involved in heart thickening and the progression to heart failure.
Approximately 65 million Americans have high blood pressure or hypertension, which can lead to cardiac hypertrophy, a thickening of the heart muscle brought on because the heart has to pump harder to get its job done. At least one fourth of people with high blood pressure have cardiac hypertrophy, which also increases the risk of heart failure or sudden death by a factor of two to three, Champion said.
In one experiment, Champion and his colleagues divided 10 to 40 male mice into two groups, one that was fed Viagra and one that received a regular diet. They then constricted the main artery in the mice, causing the heart to pump harder and resulting in a condition essentially the same as hypertrophy.
The mice who got Viagra only developed half the hypertrophy that the other animals did. The Viagra mice also showed 67 percent less muscle fibrosis (stiffening), and also had smaller hearts and improved heart function.
In another experiment, the researchers gave Viagra to part of a group of male mice that had already developed hypertrophy. After two weeks, fibrosis and muscle growth almost completely disappeared in the mice given Viagra while hearts continued to grow in the control mice.
Viagra works, both in the heart and the penis, by inhibiting an enzyme called PDE5A.
In the penis, however, PDE5A relaxes the smooth muscle, allowing the blood to flow and nature to resume its course.
By contrast, in the heart muscle, rather than producing a direct relaxation response, PDE5A helps break down cyclic GMP, a molecule that acts to curb stresses and overgrowth in the heart.
"The result is so impressive because it works on more than just one pathway," Champion said. "A boxer with just one jab in his repertoire is going to lose the fight, but if you have a good right jab, left jab and uppercut, you're going to be a much better fighter."
Experts had not previously known that PDE5A was involved in heart function. They had also suspected that excessive heart muscle growth was an adaptive response to malfunction in the heart. This study, however, indicates that not all hypertrophy is the same and that Viagra might block the "bad" hypertrophy, Champion explained.
In a way, Viagra is coming full circle. The drug was originally developed to dilate coronary blood vessels in people with angina. It didn't work for angina, but while being tested, was revealed to have the erectile dysfunction effect, for which it is now famous.
Champion believed that the effect on the heart may actually be seen in the entire class of drugs, not just Viagra. "It could very well be that Levitra or Cialis would do the same thing," he said, referring to Viagra's two competitors in the erectile dysfunction marketplace.
In general, the researchers are ahead of the game because Viagra is already approved. "The beautiful thing about this drug is we know that there are 20 million prescriptions written for Viagra. We know it to be a very safe drug," Champion said.
It may be a while, though, before Viagra as heart therapy becomes a possibility: Heart failure drug trials take time to prove measurable results.
But Champion added, "I will say, if it is half as impressive as we see in the mice, it might not take that long."
Researchers will also be looking to see if Viagra has any effect on other systems in the body
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