Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation

Incubation of rat aortas with endotoxin and interferon-gamma for 24 h resul ted in an aortic oxygen consumption that was substantially inhibited and st rongly oxygen dependent (37% inhibition at 160 muM O-2 and 62% inhibition a t 80 muM O-2 relative to untreated aortas). This respiratory inhibition was reversed by a nitric oxide (NO) scavenger (oxyhemoglobin) or by an inhibit or of inducible NO synthase [N-(3-(aminomethyl) benzyl) acetamide . 2HCl, 1 400W], but not by an inhibitor of soluble guanylate cyclase (1H-[1,2,4] oxa diazolo[4,3-a]-quinoxalin-1-one). Addition of 1 mM NO to untreated aortas c aused rapid and reversible inhibition of oxygen consumption that was greate r 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 similar to0.5 muM and 90% inhibition of ce llular 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.