"A larger-than-normal heart is a serious medical condition, known as hypertrophy, and is a common feature of heart failure that can be fatal," says study senior author and cardiologist David Kass, M.D., a professor at The Johns Hopkins University School of Medicine and its Heart Institute. Kass is also the Abraham and Virginia Weiss Professor of Cardiology at Hopkins.
Sildenafil, Kass says, was the focus of his research because it blocks or stops an enzyme, called phosphodiesterase 5 (PDE5A), involved in the breakdown of a key molecule, cyclic GMP, which serves as a "natural brake" to stresses and overgrowth in the heart. "We thought we could more strongly apply the brake on hypertrophy in the heart if we used sildenafil to prevent the breakdown of cyclic GMP," he says. The makers of the drug had no involvement in the design or support of the research. PDE5A is also the biological pathway blocked in the penis to prevent the relaxation of blood vessels and maintain erections.
The Johns Hopkins findings, to be published in the journal Nature Medicine online Jan. 23, are the first to show that sildenafil is an effective treatment for a chronic heart condition. It is also the first study to reveal that the enzyme pathway blocked by sildenafil (PDE5A), never before known to play a significant role in the heart, is active when the heart is exposed to pressure stress and hypertrophied. The results provide some of the strongest evidence to date that blocking the heart's adaptive response to hypertrophy does not harm its function but, in fact, may improve it, Kass says. Already, plans are under way by the Hopkins researchers f
Contact: David March
Johns Hopkins Medical Institutions