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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-
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-
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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