| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
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 (KATP) 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 KATP 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 KATP channels.
ATP-sensitive potassium channel; ischemia-reperfusion; phosphodiesterase-5
This article has been cited by other articles:
|
|
 |
|
  G. Szabo, T. Radovits, G. Veres, N. Krieger, S. Loganathan, P. Sandner, and M. Karck Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass Eur. J. Cardiothorac. Surg., October 1, 2009; 36(4): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. N. Salloum, V. Q. Chau, N. N. Hoke, A. Abbate, A. Varma, R. A. Ockaili, S. Toldo, and R. C. Kukreja Phosphodiesterase-5 Inhibitor, Tadalafil, Protects Against Myocardial Ischemia/Reperfusion Through Protein-Kinase G-Dependent Generation of Hydrogen Sulfide Circulation, September 15, 2009; 120(11_suppl_1): S31 - S36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Choi, J. Y. Jeong, B. J. Lim, S. Chung, Y. K. Chang, S. J. Lee, K. R. Na, S. Y. Kim, Y. T. Shin, and K. W. Lee Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats Am J Physiol Renal Physiol, August 1, 2009; 297(2): F362 - F370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reffelmann and R. A. Kloner Phosphodiesterase 5 inhibitors: are they cardioprotective? Cardiovasc Res, July 15, 2009; 83(2): 204 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ahmad, Y. Wang, A. K. Ali, and M. Ashraf Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H387 - H391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nagendran and E. D. Michelakis Mitochondrial NOS is upregulated in the hypoxic heart: implications for the function of the hypertrophied right ventricle Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1723 - H1726. [Full Text] [PDF]
|
|
|
|
|
|
A. Das, F. N. Salloum, L. Xi, Y. J. Rao, and R. C. Kukreja ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1236 - H1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xia How does Viagra protect the ischemic heart? Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1209 - H1210. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guazzi Clinical Use of Phosphodiesterase-5 Inhibitors in Chronic Heart Failure Circ Heart Fail, November 1, 2008; 1(4): 272 - 280. [Full Text] [PDF]
|
|
|
|
 |
|
 F Urdaneta, E. Lobato, T Beaver, J. Muehlschlegel, D. Kirby, C Klodell, and A Sidi Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog Perfusion, March 1, 2008; 23(2): 117 - 125. [Abstract] [PDF]
|
|
|
|
|
|
F. N. Salloum, A. Abbate, A. Das, J.-E. Houser, C. A. Mudrick, I. Z. Qureshi, N. N. Hoke, S. K. Roy, W. R. Brown, S. Prabhakar, et al. Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1398 - H1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kass, H. C. Champion, and J. A. Beavo Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation Circ. Res., November 26, 2007; 101(11): 1084 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Brown and R. L. Moore Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise J Appl Physiol, November 1, 2007; 103(5): 1894 - 1899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Natarajan, F. N. Salloum, B. J. Fisher, E. D. Ownby, R. C. Kukreja, and A. A. Fowler 3rd Activation of hypoxia-inducible factor-1 via prolyl-4 hydoxylase-2 gene silencing attenuates acute inflammatory responses in postischemic myocardium Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1571 - H1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Elrod, J. J. M. Greer, and D. J. Lefer Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H342 - H347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Shim, Y. S. Choi, Y. J. Oh, D. H. Kim, Y. W. Hong, and Y. L. Kwak Effect of oral sildenafil citrate on intraoperative hemodynamics in patients with pulmonary hypertension undergoing valvular heart surgery J. Thorac. Cardiovasc. Surg., December 1, 2006; 132(6): 1420 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Kukreja Mechanism of reactive oxygen species generation after opening of mitochondrial KATP channels Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2041 - H2043. [Full Text] [PDF]
|
|
|
|
|
|
S. Korom, S. Hillinger, M. Cardell, W. Zhai, Q. Tan, A. Dutly, B. Leskosek, and W. Weder Sildenafil extends survival and graft function in a large animal lung transplantation model Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 288 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Lobato, T. Beaver, J. Muehlschlegel, D. S. Kirby, C. Klodell, and A. Sidi Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension Br. J. Anaesth., March 1, 2006; 96(3): 317 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Brown, A. J. Chicco, K. N. Jew, M. S. Johnson, J. M. Lynch, P. A. Watson, and R. L. Moore Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat J. Physiol., December 15, 2005; 569(3): 913 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ockaili, R. Natarajan, F. Salloum, B. J. Fisher, D. Jones, A. A. Fowler III, and R. C. Kukreja HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H542 - H548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Qin, X.-M. Yang, L. Cui, S. D. Critz, M. V. Cohen, N. C. Browner, T. M. Lincoln, and J. M. Downey Exogenous NO triggers preconditioning via a cGMP- and mitoKATP-dependent mechanism Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H712 - H718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Das, R. Ockaili, F. Salloum, and R. C. Kukreja Protein kinase C plays an essential role in sildenafil-induced cardioprotection in rabbits Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1455 - H1460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O'Rourke Evidence for Mitochondrial K+ Channels and Their Role in Cardioprotection Circ. Res., March 5, 2004; 94(4): 420 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Jones, J. J. M. Greer, A. K. Kakkar, P. D. Ware, R. H. Turnage, M. Hicks, R. van Haperen, R. de Crom, S. Kawashima, M. Yokoyama, et al. Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H276 - H282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Oldenburg, Q. Qin, T. Krieg, X.-M. Yang, S. Philipp, S. D. Critz, M. V. Cohen, and J. M. Downey Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H468 - H476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Brown, K. N. Jew, G. C. Sparagna, T. I. Musch, and R. L. Moore Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart J Appl Physiol, December 1, 2003; 95(6): 2510 - 2518. [Abstract] [Full Text]
|
|
|
|
|
|
R. C Kukreja, R. Ockaili, F. Salloum, and L. Xi Sildenafil-induced cardioprotection in rabbits Cardiovasc Res, December 1, 2003; 60(3): 700 - 701. [Full Text] [PDF]
|
|
|
|
|
|
T. Reffelmann and R. A Kloner Cardiovascular effects of sildenafil in experimental ischemia-reperfusion (reply to "Sildenafil-induced cardioprotection in rabbits, by Kukreja, R.C., Ockaili, R., Salloum, F., Xi, L.") Cardiovasc Res, December 1, 2003; 60(3): 702 - 703. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
