Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial K(ATP) channels in rabbits.
Sildenafil citrate (Viagra) is the pharmacological agent used to treat erectile dysfunction in men. Because this drug has a vasodilatory effect, we hypothesized that such an action may induce a preconditioning-like cardioprotective effect via opening of mitochondrial ATP-sensitive K (K(ATP)) channels. Rabbits were treated with sildenafil citrate (0.7 mg/kg iv) either 30 min (acute phase) or 24 h (delayed phase) before 30 min of ischemia and 3 h of reperfusion. Mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg iv) was given 10 min before ischemia-reperfusion. Infarct size was measured by tetrazolium staining. Sildenafil caused reduction in arterial blood pressure within 2 min of treatment, which returned to nearly baseline levels 3 min later. The infarct size (% risk area, means +/- SE) reduced from 33.8 +/- 1.7 in control rabbits to 10.8 +/- 0.9 during the acute phase (68% reduction, P < 0.05) and 19.9 +/- 2.0 during the delayed phase (41% reduction, P < 0.05). 5-HD abolished protection with an increase in infarct size to 35.6 +/- 0.4% and 36.8 +/- 1.6% during the acute and delayed phase, respectively (P < 0.05). Similar acute and delayed cardioprotective effects were observed when sildenafil was administered orally. Systemic hemodynamics also decreased after oral administration of the drug. However, these changes were mild and occurred slowly. For the first time, we demonstrate that sildenafil induces acute and delayed protective effects against ischemia-reperfusion injury, which are mediated by opening of mitochondrial K(ATP) channels.
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Ramzi
R
Ockaili
Fadi
F
Salloum
John
J
Hawkins
Rakesh C
RC
Kukreja
D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D010879:Piperazines / Q000494:pharmacology*; D015221:Potassium Channels; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D008565:Membrane Proteins; D010879:Piperazines; D015221:Potassium Channels; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D000068677:Sildenafil Citrate