© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Preservation of NO production by statins in the treatment of heart failure
aDepartment of Physiology, New York Medical College, Basic Sciences Building, Valhalla, NY 10595, USA
bBrigham and Women's Hospital, Harvard Medical School, Boston, MA 01772, USA
*Corresponding author. Tel.: +1-914-594-3633; fax: +1-914-594-4108. Email address: thomas_hintze{at}nymc.edu
Objective: Because statins promote endogenous nitric oxide (NO) production in vessels by increasing endothelial nitric oxide synthase (eNOS), we evaluated the clinical benefit and efficiency of simvastatin in preventing the decrease in NO control of coronary blood flow (CBF), NO regulation of myocardial oxygen consumption (MVO2) and decreased nitrite production in coronary microvessels, associated with pacing-induced heart failure (HF). Methods: Dogs (n = 17) were instrumented for measurement of coronary blood flow and left ventricular end diastolic pressure (LVEDP). HF was induced by pacing. Ten dogs were given simvastatin 20 mg/kg/day orally (HF+SIMVA) from the 10th day of pacing. Results: HF+SIMVA had a lower LVEDP at 4 weeks of pacing (18±1 vs. 25±1 mm Hg, p<0.05), and the NO-dependent coronary vasodilation to veratrine was preserved compared to HF (p<0.05). In coronary microvessels, SIMVA potentiated nitrite production compared to HF (p<0.05) and enhanced the NO-dependent decrease in MVO2 in cardiac tissue in response to 10–4 mol/l bradykinin, which was markedly blunted in HF (p<0.05). Using Western blotting, there was a reduction in eNOS protein during HF that was preserved at 4–5 weeks of pacing during treatment with SIMVA. Conclusions: Simvastatin maintained NO production by coronary vessels and NO bioactivity during pacing-induced dilated cardiomyopathy. Targeting the endothelium, which participates in the control of myocardial metabolism by NO, may be an important mechanism of action of statins in the treatment of heart failure.
KEYWORDS Nitric oxide; Heart failure; Statins; Hypertrophy; Oxygen consumption
Time for primary review 27 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Suzuki, V. Iyer, T. Cimato, and J. M. Canty Jr Pravastatin Improves Function in Hibernating Myocardium by Mobilizing CD133+ and cKit+ Bone Marrow Progenitor Cells and Promoting Myocytes to Reenter the Growth Phase of the Cardiac Cell Cycle Circ. Res., January 30, 2009; 104(2): 255 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Adam, H.-R. Neuberger, M. Bohm, and U. Laufs Prevention of Atrial Fibrillation With 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Circulation, September 16, 2008; 118(12): 1285 - 1293. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ramasubbu, J. Estep, D. L. White, A. Deswal, and D. L. Mann Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 415 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. H. Zucker Novel Mechanisms of Sympathetic Regulation in Chronic Heart Failure Hypertension, December 1, 2006; 48(6): 1005 - 1011. [Full Text] [PDF]
|
|
|
|
|
|
E. R. Schwarz, S. Rastogi, V. Kapur, N. Sulemanjee, and J. J. Rodriguez Erectile Dysfunction in Heart Failure Patients J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1111 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Post and B. Pieske Arginase: a modulator of myocardial function Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1747 - H1748. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Lionetti, A. Linke, M. P. Chandler, M. E. Young, M. S. Penn, S. Gupte, C. d'Agostino, T. H. Hintze, W. C. Stanley, and F. A. Recchia Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure Cardiovasc Res, June 1, 2005; 66(3): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schafer, D. Fraccarollo, M. Eigenthaler, P. Tas, A. Firnschild, S. Frantz, G. Ertl, and J. Bauersachs Rosuvastatin Reduces Platelet Activation in Heart Failure: Role of NO Bioavailability Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Wainwright Statins-is there no end to their usefulness? Cardiovasc Res, February 1, 2005; 65(2): 296 - 298. [Full Text] [PDF]
|
|