Straight to the heart with Viagra

Sildenafil, a popular drug used for erectile dysfunction, aids the enlargement of one organ but may inhibit that of another. New research by Eiki Takimoto and colleagues¹ demonstrates that sildenafil suppresses myocardial hypertrophy in the face of chronic increased cardiac afterload. Their findings also provide clues as to how cardiac myocyte hypertrophy occurs.

Cardiac hypertrophy usually occurs in patients to compensate for increased cardiac afterload resulting from systemic hypertension. Unfortunately, this can be maladaptive, resulting in cardiac ischemia and heart failure. The process is mediated by proteins that signal and respond to these changes in pressure; some of these proteins have been proposed as potential therapeutic targets,² but few have been directly studied with drug inhibition.

One of these is guanosine 3́,5́-cyclic monophosphate (cGMP). Sildenafil is an inhibitor of the phosphodiesterase-5A (PDE5A) enzyme, which metabolizes cGMP inside cells. To investigate the effect of sildenafil on cardiac hypertrophy, the researchers constricted the transverse aorta of mice to expose them to increased cardiac afterload. They found that mice given sildenafil did not develop cardiac hypertrophy. Moreover, in mice that acquired cardiac hypertrophy (mean 63% increase in heart mass), sildenafil treatment reduced the hypertrophy to baseline levels.

Takimoto and colleagues went on to show that by inhibiting PDE5A and thereby raising the levels of cGMP inside cells, the activity of intracellular protein cGMP-dependent protein kinase G type-1 (PKG-1) was increased. The role of this protein in regulating cardiac hypertrophy is unclear, but the results suggest that it could be a target for future drug development.

Figure. Is sildenafil good for the heart? Photo by: Corbis/Magma