Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide

Nitric oxide (NO) inhibited the respiration rate of mitochondria isolated from rat heart at sub-micromolar concentrations of NO. The inhibition was rapidly and completely reversible, indicating that NO does not damage mitochondria. The sensitivity of respiration to NO depended on the oxygen concentration, substrate type and respiratory state of the mitochondria, consistent with NO competing with oxygen at cytochrome oxidase. Mitochondria catalysed a rapid rate of NO breakdown, which was greater in the absence of oxygen and was partly inhibited by cyanide and azide, suggesting that at least part of the NO breakdown was due to reduction of NO by cytochrome oxidase. The rapid rate of this breakdown suggests that mitochondrial breakdown of NO may be significant physiologically.