Viagra against heart failure: Researchers throw light on the mechanism

Sildenafil inhibits a specific enzyme (phosphodiesterase 5 A), which causes the increased formation of a messenger substance (cGMP). The messenger substance activates the enzyme protein kinase G, which attaches phosphate groups to certain proteins. This so-called phosphorylation causes blood vessels to relax, which was why the "potency pill" Viagra originally came onto the market. The Bochum and Rochester researchers found that the cardiac muscle protein titin is also phosphorylated through the same mechanism. "The titin molecules are similar to rubber bands" explains the Bochum physiologist. "They contribute decisively to the stiffness of the cardiac walls." The activity of the protein kinase G causes titin to relax. This makes the cardiac walls more elastic. The effect occurs within minutes of administering the drug.

"Of all the patients aged over 60 who are in hospital because of a weak heart, half suffer from diastolic heart failure" explains Linke. "Although we know that the decreased distensibility of the cardiac walls is the cause, the disease cannot be treated properly with today's medicines." In the so-called "Relax" study of the Heart Failure Network, the efficacy of sildenafil in people is already being tested. "If, for the first time, the drug is found to have a positive effect on heart failure, we would already have a molecular mechanism on hand to explain the effect" says Linke.

More information: K. Bishu, N. Hamdani, S.F. Mohammed, M. Kruger, T. Ohtani, O. Ogut, F.V. Brozovich, J.C. Burnett, W.A. Linke, M.M. Redfield (2011): Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo, Circulation, doi: 10.1161/CIRCULATIONAHA.111.048520

Journal reference: Circulation

Provided by Ruhr-University Bochum