Sildenafil appears to delay dangerous heart muscle expansion in mice
MONDAY, Jan. 5 (HealthDay News) -- Tests in mouse hearts show that sildenafil, the key ingredient in Viagra, may shield hearts from damage caused by high blood pressure, a new study suggests.
Investigators said that sildenafil appears to influence RGS2, a single protein essential in the reactions that initially protect the heart's blood-pumping function from spiraling into heart failure. The findings, published online Monday in The Journal of Clinical Investigation, suggest that sildenafil may prove useful in the treatment or prevention of heart damage due to chronic high blood pressure.
"Sildenafil clearly prolongs the protective effects of RGS2 in mouse hearts," senior investigator Dr. David Kass, a cardiologist and professor of medicine at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute in Baltimore, said in a Hopkins news release.
After a week of inducing high blood pressure in the mice, the team found that the hearts engineered to lack RGS2, or regulator of G-protein signaling 2, expanded in weight by 90 percent, and almost half of the experiment animals died of heart failure. In the mice with RGS2, the dangerous muscle expansion, known as hypertrophy, was delayed, growing by only 30 percent, the researchers found, and none of those mice died.
Later testing showed that treating hypertensive mice that had RGS2 with sildenafil showed enhanced buffering, less hypertrophy, and stronger heart muscle contraction and relaxation. In addition, these mice showed as much as 10 times lower stress-related enzyme activity compared to their untreated counterparts. The study also found that sildenafil had no effect in mice lacking RGS2.
The study involved more than a half-dozen experiments, all performed within the last three years, designed to zero in on RGS2's role in stalling hypertrophy.
"The evidence is piling up that unbridled Gq signaling is driving a central biological chain reaction in heart failure, and that by extending the protective effects of RGS2 or by developing a test for its presence, researchers can develop new therapies or improve existing ones, including ACE inhibitors and possibly sildenafil, for people with heart failure who will benefit most," Kass said.
Doctors currently use so-called ACE inhibitor and ARB inhibitor drugs to block Gq signaling. These drugs are the most common treatment for heart failure, which afflicts more than 5 million Americans each year, killing more than a quarter million of them, according to the study.
For more on the symptoms of heart failure, go to American Heart Association.
-- HealthDay staff
SOURCE: Johns Hopkins University School of Medicine, news release, Jan. 2, 2009
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