Viagra may protect the heart from effects of high blood pressure

Researchers from Johns Hopkins have found the reason that sildenafil, marketed as Viagra, has heart-protective properties and why the drug may one day be used to either treat or prevent damage to the heart caused by chronic high blood pressure. The findings were published recently in the Journal of Clinical Investigation.

Sildenafil apparently effects a single protein, called RGS2, which is involved in the chain reactions that prevent heart failure in a damaged heart. Experimenting in mice, the team of heart experts first established that after a week of induced high blood pressure, the hearts of animals engineered to lack RGS2, or regulator of G-protein signaling 2, quickly expanded in weight by 90 percent. Almost half the mice died of heart failure. In mice with RGS2, by contrast, the dangerous muscle expansion, known as hypertrophy, was delayed, growing only 30 percent, and no mice died.

Subsequent tests treating hypertensive mice that had RGS2 with sildenafil showed enhanced buffering, with less hypertrophy, stronger heart muscle contraction and relaxation, and as much as 10 times lower stress-related enzyme activity compared to their untreated counterparts. In mice lacking RGS2, sildenafil had no effect.

RGS2 is stimulated by an enzyme, protein kinase G, whose action is, in turn, raised by countering the activity of another enzyme, phosphodiesterase 5 (PDE5A). Sildenafil's ability to block PDE5A was shown by Kass and his team in 2005 to be responsible for blunting hypertrophy due to high blood pressure in mice and offsetting similar, adrenaline-stimulated heart stress in people.

Kass says RGS2 acts like a short-term reset mechanism in the heart, recoupling G proteins that if left alone stimulate the heart's response to high blood pressure. And without the "reset," a cascade of reactions known as Gq signaling leads to scar tissue formation, hypertrophy and heart failure.