Skip to main content
SpringerLink
Log in

Synergistic Effects of Atorvastatin and Sildenafil in Cardioprotection—Role of NO

  • Editorial
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Edwards P, Ericsson J. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway. Ann Rev Biochem 1999;68:157–185.

    Article  CAS  PubMed  Google Scholar 

  2. Lefer AM, Campbell B, Shin Y, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic–reperfused myocardium in normocholesterolemic rat hearts. Circulation 1999;100:178–184.

    CAS  PubMed  Google Scholar 

  3. Scalia R, Gooszen SP, Jones M, et al. Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein E-deficient mice. Circulation 2001; 103:2598–2603.

    CAS  PubMed  Google Scholar 

  4. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Inv. 1998;101:2711–2719.

    CAS  Google Scholar 

  5. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998;97:1129–1135.

    CAS  PubMed  Google Scholar 

  6. Kureishi Y, Shiojima I, Bialik A, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;9:1004–1010.

    Google Scholar 

  7. Bell RM, Yellon DM. Atorvastatin, administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by up-regulating a pro-survival pathway. J Am Coll Cardiol 2003;41:508–515.

    Article  CAS  PubMed  Google Scholar 

  8. Chou E, Salloum F, Ockaili R, Bremer Y, Kukreja RC. Atorvastatin triggers early and delayed myocardial protection in-vivo: role of nitric oxide and mitochondrial KATP channels Circulation 2003;102:(Suppl)II–157 (Abstract).

  9. Chen JC, Huang KC, Lin WW. HMG-CoA reductase inhibitors upregulate heme oxygenase-1 expression in murine RAW264.7 macrophages via ERK, p38 MAPK and protein kinase G pathways. Cell Signal 2006;18:32–39.

    Article  CAS  PubMed  Google Scholar 

  10. Hayashidani S, Tsutsui H, Shiomi T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 2002;105:868–873.

    Article  CAS  PubMed  Google Scholar 

  11. Landmesser U, Engberding N, Bahlmann FH, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 2004;110:1933–1939.

    Article  CAS  PubMed  Google Scholar 

  12. Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation 2001;104:982–985.

    CAS  PubMed  Google Scholar 

  13. Mozaffarian D, Nye R, Levy WC. Statin therapy is associated with lower mortality among patients with severe heart failure. Am J Cardiol 2004;93:1124–1129.

    Article  CAS  PubMed  Google Scholar 

  14. Chan AW, Bhatt DL, Chew DP, et al. Early and sustained survival benefit associated with statin therapy at the time of percutaneous coronary intervention. Circulation 2002;105:691–696.

    Article  CAS  PubMed  Google Scholar 

  15. Pan W, Pintar T, Anton J, Lee V-V, Vaughn WK, Collard CD. Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery. Circulation 2004(11 Suppl 1); 110:II45–II49.

    PubMed  Google Scholar 

  16. Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996;8:47–52.

    CAS  PubMed  Google Scholar 

  17. Porst H, Rosen R, Padma-Nathan H, et al. The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial. Int J Impot Res 2001;13:192–199.

    Article  CAS  PubMed  Google Scholar 

  18. Francis SH, Corbin JD. Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci 1999;36:275–328.

    Article  CAS  PubMed  Google Scholar 

  19. Senzaki H, Juang GJ, Isoda T, et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. Faseb J 2001;15:1718–1726.

    Article  CAS  PubMed  Google Scholar 

  20. Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor, sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis: essential role of NO signaling. J Biol Chem 2005;280:12944–12955.

    Article  CAS  PubMed  Google Scholar 

  21. Saenz de Tejada I, Angulo J, Cuevas P, et al. The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res 2001;13:282–290.

    Article  Google Scholar 

  22. Eardley I, Cartledge J. Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract 2002;56:300–304.

    CAS  PubMed  Google Scholar 

  23. Kukreja RC, Salloum F, Das A, et al. Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications. Vascul Pharmacol 2005;42:219–232.

    Article  CAS  PubMed  Google Scholar 

  24. Kukreja RC, Ockaili R, Salloum F, et al. Cardioprotection with phosphodiesterase-5 inhibition—a novel preconditioning strategy. J Mol Cell Cardiol 2004;36:165–173.

    Article  CAS  PubMed  Google Scholar 

  25. Ockaili R, Salloum F, Hawkin J, Kukreja RC. Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits. Am J Physiol 2002;283:H1263–H1269.

    CAS  Google Scholar 

  26. Bremer YA, Salloum F, Ockaili R, Chou E, Moskowitz WB, Kukreja RC. Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits. Pediatr Res 2005;57:22–27.

    Article  CAS  PubMed  Google Scholar 

  27. Salloum F, Yin C, Xi L, Kukreja RC. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Circ Res 2003;92:595–597.

    Article  CAS  PubMed  Google Scholar 

  28. Salloum F, Xi L, Ockaili R, Yin C, Kukreja RC. Delayed pharmacological preconditioning with Viagra (Sildenafil) against myocardial infarction is independent of p38 MAPK signaling pathway. Circulation 2002;102(Suppl):II–378.

    Google Scholar 

  29. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005;111:1601–1610.

    Article  CAS  PubMed  Google Scholar 

  30. Nagy O, Hajnal A, Parratt JR, Agnes V. Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24 h after oral administration in dogs. Br J Pharmacol 2004;141:549–551.

    Article  CAS  PubMed  Google Scholar 

  31. Takimoto E, Champion HC, Li M, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 2005;11:214–222.

    Article  CAS  PubMed  Google Scholar 

  32. Das A, Ockaili R, Salloum F, Kukreja RC. Protein kinase C plays an essential role in sildenafil-induced cardioprotection in rabbits. Am J Physiol 2004;286:455–460.

    Google Scholar 

  33. Rosanio S, Ye Y, Atar S, Rahman AM, Freeberg SY, Huang M-H, Uretsky BF, Birnbaum Y. Enhanced cardioprotection against Ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin. Cardiovasc Drug Therap 2006 In press.

  34. Vinten-Johansen J, Zhao ZQ, Corvera JS, et al. Adenosine in myocardial protection in on-pump and off-pump cardiac surgery. Ann Thorac Surg 2003;75:S691–S699.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Mashall Street, Room 7-046, Richmond, VA, 23298-0281, USA

    Rakesh C. Kukreja PhD

  2. Division of Cardiology, Virginia Commonwealth University, 1101 East Mashall Street, Room 7-046, Box 980281, Richmond, VA, 23298-0281, USA

    Rakesh C. Kukreja PhD

Authors
  1. Rakesh C. Kukreja PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rakesh C. Kukreja PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kukreja, R.C. Synergistic Effects of Atorvastatin and Sildenafil in Cardioprotection—Role of NO. Cardiovasc Drugs Ther 20, 5–8 (2006). https://doi.org/10.1007/s10557-006-7298-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-006-7298-7

Search

Navigation