Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Martin, C; Schulz, R; Post, H; Gres, P; Heusch, G.
Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia.
Am J Physiol Heart Circ Physiol. 2003; 284(6):H2320-H2324
Doi: 10.1152/ajpheart.01122.2002
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- Co-Autor*innen der Med Uni Graz
- Post Heiner
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- Abstract:
- Nitric oxide (NO) is involved in the control of myocardial metabolism. In normoperfused myocardium, NO synthase inhibition shifts myocardial metabolism from free fatty acid (FFA) toward carbohydrate utilization. Ischemic myocardium is characterized by a similar shift toward preferential carbohydrate utilization, although NO synthesis is increased. The importance of NO for myocardial metabolism during ischemia has not been analyzed in detail. We therefore assessed the influence of NO synthase inhibition with N(G)-nitro-l-arginine (l-NNA) on myocardial metabolism during moderate ischemia in anesthetized pigs. In control animals, the increase in left ventricular pressure with l-NNA was mimicked by aortic constriction. Before ischemia, l-NNA decreased myocardial FFA consumption (MV(FFA); P < 0.05), while consumption of carbohydrate and O(2) (MVo(2)) remained constant. ATP equivalents [calculated with the assumption of complete oxidative substrate decomposition (ATP(eq))] decreased with l-NNA (P < 0.05), associated with a decrease of regional myocardial function (P < 0.05). In contrast, aortic constriction had no effect on MV(FFA), while MVo(2) increased (P < 0.05) and ATP(eq) and regional myocardial function remained constant. During ischemia, alterations in myocardial metabolism were similar in control and l-NNA-treated animals: MV(FFA) decreased (P < 0.05) and net lactate consumption was reversed to net lactate production (P < 0.05). Regional myocardial function was decreased (P < 0.05), although more markedly in animals receiving l-NNA (P < 0.05). We conclude that the efficiency of oxidative metabolism was impaired by l-NNA per se, paralleled by impaired regional myocardial function. During ischemia, l-NNA had no effect on myocardial substrate consumption, indicating that NO synthases were no longer effectively involved in the control of myocardial metabolism.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Coronary Circulation - drug effects
- Energy Metabolism - drug effects
- Enzyme Inhibitors - pharmacology
- Fatty Acids, Nonesterified - metabolism
- Glucose - metabolism
- Lactic Acid - metabolism
- Myocardial Ischemia - metabolism
- Myocardium - metabolism
- Nitric Oxide Synthase - antagonists and inhibitors
- Nitroarginine - pharmacology
- Oxygen Consumption - drug effects
- Swine - drug effects
- Swine, Miniature - drug effects
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- Find related publications in this database (Keywords)
- nitric oxide
- free fatty acids
- glucose
- lactate
- myocardial ischemia