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Am J Physiol Heart Circ Physiol 281: H2256-H2260, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 6, H2256-H2260, December 2001

SPECIAL TOPIC
Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation

Vilmante Borutaite1, Anita Matthias1, Hatty Harris1, Salvador Moncada2, and Guy C. Brown1

1 Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW; and 2 Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom

Incubation of rat aortas with endotoxin and interferon-gamma for 24 h resulted in an aortic oxygen consumption that was substantially inhibited and strongly oxygen dependent (37% inhibition at 160 µM O2 and 62% inhibition at 80 µM O2 relative to untreated aortas). This respiratory inhibition was reversed by a nitric oxide (NO) scavenger (oxyhemoglobin) or by an inhibitor of inducible NO synthase [N-(3-(aminomethyl)benzyl)acetamide · 2HCl, 1400W], but not by an inhibitor of soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one). Addition of 1 µM NO to untreated aortas caused rapid and reversible inhibition of oxygen consumption that was greater at lower oxygen concentrations. Incubation of endothelial cells isolated from rat aortas with endotoxin and interferon-gamma for 24 h resulted in a steady-state NO concentration of ~0.5 µM and 90% inhibition of cellular oxygen consumption that was immediately reversed by an NO scavenger (oxyhemoglobin). These results suggest that during inflammation and sepsis, tissue respiration may be substantially reduced due to inhibition by NO of cytochrome oxidase.

aorta; endothelial cells; mitochondria; inducible nitric oxide synthase; oxygen


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