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: 290/4/H1721    most recent 00745.2005v1 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 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 (2) Citing Articles via Google Scholar Google Scholar Articles by d'Agostino, C. Articles by Recchia, F. A. Search for Related Content PubMed PubMed Citation Articles by d'Agostino, C. Articles by Recchia, F. A.

REPORT

Altered cardiac metabolic phenotype after prolonged inhibition of NO synthesis in chronically instrumented dogs

¹Department of Physiology, New York Medical College, Valhalla, New York; ²Scuola Superiore Sant'Anna, Settore di Medicina, Pisa, Italy; and ³Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio

Submitted 14 July 2005 ; accepted in final form 10 November 2005

Acute inhibition of nitric oxide (NO) synthase causes a reversible alteration in myocardial substrate metabolism. We tested the hypothesis that prolonged NO synthase inhibition alters cardiac metabolic phenotype. Seven chronically instrumented dogs were treated with N-nitro-L-arginine methyl ester (L-NAME, 35 mg·kg^–1·day^–1 po) for 10 days to inhibit NO synthesis, and seven were used as controls. Cardiac free fatty acid, glucose, and lactate oxidation were measured by infusion of [³H]oleate, [¹⁴C]glucose, and [¹³C]lactate, respectively. After 10 days of L-NAME administration, despite no differences in left ventricular afterload, cardiac O₂ consumption was significantly increased by 30%, consistent with a marked enhancement in baseline oxidation of glucose (6.9 ± 2.0 vs. 1.7 ± 0.5 µmol·min^–1·100 g^–1, P < 0.05 vs. control) and lactate (21.6 ± 5.6 vs. 11.8 ± 2.6 µmol·min^–1·100 g^–1, P < 0.05 vs. control). When left ventricular afterload was increased by ANG II infusion to stimulate myocardial metabolism, glucose oxidation was augmented further in the L-NAME than in the control group, whereas free fatty acid oxidation decreased. Exogenous NO (diethylamine nonoate, 0.01 µmol·kg^–1·min^–1 iv) could not reverse this metabolic alteration. Consistent with the accelerated rate of carbohydrate oxidation, total myocardial pyruvate dehydrogenase activity and protein expression were higher (38 and 34%, respectively) in the L-NAME than in the control group. Also, protein expression of the constitutively active glucose transporter GLUT-1 was significantly elevated (46%) vs. control. We conclude that prolonged NO deficiency causes a profound alteration in cardiac metabolic phenotype, characterized by selective potentiation of carbohydrate oxidation, that cannot be reversed by a short-term infusion of exogenous NO. This phenomenon may constitute an adaptive mechanism to counterbalance cardiac mechanical inefficiency.

heart; metabolism; nitric oxide

This article has been cited by other articles:

				P. F. Soto, P. Herrero, K. B. Schechtman, A. D. Waggoner, J. M. Baumstark, A. A. Ehsani, and R. J. Gropler Exercise training impacts the myocardial metabolism of older individuals in a gender-specific manner Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H842 - H850. [Abstract] [Full Text] [PDF]

				J. G. Williams, C. Ojaimi, K. Qanud, S. Zhang, X. Xu, F. A. Recchia, and T. H. Hintze Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2516 - H2523. [Abstract] [Full Text] [PDF]

				D. V. Cuong, M. Warda, N. Kim, W. S. Park, J. H. Ko, E. Kim, and J. Han Dynamic changes in nitric oxide and mitochondrial oxidative stress with site-dependent differential tissue response during anoxic preconditioning in rat heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1457 - H1465. [Abstract] [Full Text] [PDF]