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: 289/6/H2616    most recent 00546.2005v1 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 ISI 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 ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Liu, Y.-H. Articles by Yang, X.-P. Search for Related Content PubMed PubMed Citation Articles by Liu, Y.-H. Articles by Yang, X.-P.

Role of inducible nitric oxide synthase in cardiac function and remodeling in mice with heart failure due to myocardial infarction

¹Hypertension and Vascular Research Division, Department of Internal Medicine; and ²Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, Michigan

Submitted 23 May 2005 ; accepted in final form 25 July 2005

Using inducible nitric oxide (NO) synthase (iNOS) knockout mice (iNOS^–/–), we tested the hypotheses that 1) lack of iNOS attenuates cardiac remodeling and dysfunction and improves cardiac reserve postmyocardial infarction (MI), an effect that is partially mediated by reduction of oxidative stress due to reduced interaction between NO and reactive oxygen species (ROS); and 2) the cardioprotection afforded by iNOS deletion is eliminated by N-nitro-L-arginine methyl ester (L-NAME) due to inhibition of endothelial NOS (eNOS) and neuronal NOS (nNOS). MI was induced by ligating the left anterior descending coronary artery. Male iNOS^–/– mice and wild-type controls (WT, C57BL/6J) were divided into sham MI, MI+vehicle, and MI+L-NAME (100 mg·kg^–1·day^–1 in drinking water for 8 wk). Cardiac function was evaluated by echocardiography. Left ventricular (LV) maximum rate of rise of ventricular pressure divided by pressure at the moment such maximum occurs (dP/dt/instant pressure) in response to isoproterenol (100 ng·kg^–1·min^–1 iv) was measured with a Millar catheter. Collagen deposition, myocyte cross-sectional area, and expression of nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE), markers for ROS, were determined by histopathological and immunohistochemical staining. We found that the MI-induced increase in LV chamber dimension and the decrease in ejection fraction, an index of systolic function, were less severe in iNOS^–/– compared with WT mice. L-NAME worsened LV remodeling and dysfunction further, and these detrimental effects were also attenuated in iNOS^–/– mice, associated with better preservation of cardiac function. Lack of iNOS also reduced nitrotyrosine and 4-HNE expression after MI, indicating reduced oxidative stress. We conclude that iNOS does not seem to be a pathological mediator of heart failure; however, the lack of iNOS improves cardiac reserve post-MI, particularly when constitutive NOS isoforms are blocked. Decreased oxidative stress and other adaptive mechanisms independent of NOS may be partially responsible for such an effect, which needs to be studied further.

oxidative stress; reactive oxygen species; ejection time

This article has been cited by other articles:

				R. LoPresti, A. Catania, T. D'Amico, M. Montana, M. Caruso, and G. Caimi Oxidative Stress in Young Subjects With Acute Myocardial Infarction: Evaluation at the Initial Stage and After 12 Months Clinical and Applied Thrombosis/Hemostasis, October 1, 2008; 14(4): 421 - 427. [Abstract] [PDF]

				J. Zhang, A. Knapton, S. E. Lipshultz, J. L. Weaver, and E. H. Herman Isoproterenol-induced Cardiotoxicity in Sprague-Dawley Rats: Correlation of Reversible and Irreversible Myocardial Injury with Release of Cardiac Troponin T and Roles of iNOS in Myocardial Injury Toxicol Pathol, February 1, 2008; 36(2): 277 - 278. [Abstract] [Full Text] [PDF]

				W. D. Gilson, F. H. Epstein, Z. Yang, Y. Xu, K.-M. R. Prasad, M.-C. Toufektsian, V. E. Laubach, and B. A. French Borderzone Contractile Dysfunction Is Transiently Attenuated and Left Ventricular Structural Remodeling Is Markedly Reduced Following Reperfused Myocardial Infarction in Inducible Nitric Oxide Synthase Knockout Mice J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1799 - 1807. [Abstract] [Full Text] [PDF]

				A. Robinet, H. Millart, F. Oszust, W. Hornebeck, and G. Bellon Binding of elastin peptides to S-Gal protects the heart against ischemia/reperfusion injury by triggering the RISK pathway FASEB J, July 1, 2007; 21(9): 1968 - 1978. [Abstract] [Full Text] [PDF]

				P. Zhang, X. Xu, X. Hu, E. D. van Deel, G. Zhu, and Y. Chen Inducible Nitric Oxide Synthase Deficiency Protects the Heart From Systolic Overload-Induced Ventricular Hypertrophy and Congestive Heart Failure Circ. Res., April 13, 2007; 100(7): 1089 - 1098. [Abstract] [Full Text] [PDF]

				X. Zhao, Y.-R. Chen, G. He, A. Zhang, L. J. Druhan, A. R. Strauch, and J. L. Zweier Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heart Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1541 - H1550. [Abstract] [Full Text] [PDF]