HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1398    most recent ajpheart.91438.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Salloum, F. N. Articles by Kukreja, R. C. Search for Related Content PubMed PubMed Citation Articles by Salloum, F. N. Articles by Kukreja, R. C.

Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice

Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia

Submitted 11 December 2007 ; accepted in final form 14 January 2008

We tested the hypothesis that chronic treatment with sildenafil attenuates myocardial infarction (MI)-induced heart failure. Sildenafil has potent protective effects against necrosis and apoptosis following ischemia-reperfusion in the intact heart and cardiomyocytes. ICR mice underwent MI by left anterior descending coronary artery ligation and were treated with sildenafil (0.71 mg/kg bid) or saline for 4 wk. Infarct size (IS) was measured 24 h postinfarction, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) were measured by echocardiography. Sildenafil reduced IS (40.0 ± 4.6%) compared with that in saline (69.6 ± 4.1%, P < 0.05). N^G-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor (15 mg/kg bid), blocked the protective effect of sildenafil (IS, 60.2 ± 1.6%, P < 0.05 vs. sildenafil). Western blot analysis revealed a significant increase in endothelial NOS/inducible NOS proteins 24 h post-MI after treatment with sildenafil versus saline. Apoptosis decreased from 2.4 ± 0.3% with saline to 1.2 ± 0.1% with sildenafil (P < 0.05) on day 7 and from 2.0 ± 0.2% with saline to 1.2 ± 0.1% with sildenafil on day 28 (P < 0.05), which was associated with an early increase in the Bcl-2-to-Bax ratio. LVEDD increased from baseline value of 3.6 ± 0.1 to 5.2 ± 0.2 and to 5.5 ± 0.1 mm on days 7 and 28, respectively, with saline (P < 0.05) but was attenuated to 4.4 ± 0.2 and 4.4 ± 0.1 mm following sildenafil treatment on days 7 and 28, respectively (P > 0.05 vs. baseline). FS significantly improved post-MI with sildenafil. A marked decline in cardiac hypertrophy was observed with sildenafil, which paralleled a reduction in pulmonary edema. Survival rate was lower with saline (36%) compared with sildenafil (93%, P < 0.05). Sildenafil attenuates ischemic cardiomyopathy in mice by limiting necrosis and apoptosis and by preserving left ventricular function possibly through a nitric oxide-dependent pathway.

phosphodiesterase inhibitors; heart failure; ischemic injury; vasodilatation; nitric oxide; guanosine 3',5'-cyclic monophosphate; apoptosis; remodeling

This article has been cited by other articles:

				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]

				F. Vandeput, J. Krall, R. Ockaili, F. N. Salloum, V. Florio, J. D. Corbin, S. H. Francis, R. C. Kukreja, and M. A. Movsesian cGMP-Hydrolytic Activity and Its Inhibition by Sildenafil in Normal and Failing Human and Mouse Myocardium J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 884 - 891. [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]

				M. M. Hoeper, J. A. Barbera, R. N. Channick, P. M. Hassoun, I. M. Lang, A. Manes, F. J. Martinez, R. Naeije, H. Olschewski, J. Pepke-Zaba, et al. Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. J. Am. Coll. Cardiol., June 30, 2009; 54(1 Suppl): S85 - S96. [Abstract] [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]

				M. Kuhn Cardiac anti-remodelling effects of phosphodiesterase type 5 inhibitors: afterload-(in)dependent? Cardiovasc Res, April 1, 2009; 82(1): 4 - 6. [Full Text] [PDF]

				T. Nagayama, S. Hsu, M. Zhang, N. Koitabashi, D. Bedja, K. L. Gabrielson, E. Takimoto, and D. A. Kass Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J. Am. Coll. Cardiol., January 13, 2009; 53(2): 207 - 215. [Abstract] [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]

				A. Abbate, F. N. Salloum, E. Vecile, A. Das, N. N. Hoke, S. Straino, G. G.L. Biondi-Zoccai, J.-E. Houser, I. Z. Qureshi, E. D. Ownby, et al. Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction Circulation, May 20, 2008; 117(20): 2670 - 2683. [Abstract] [Full Text] [PDF]