On the mechanism by which vascular endothelial cells regulate their oxygen consumption

Emilio Clementi, Guy Charles Brown, Neale Foxwell, Salvador Moncada

Research output: Contribution to journalArticle


Two enzymes, soluble guanylyl cyclase and cytochrome c oxidase, have been shown to be exquisitely sensitive to nitric oxide (NO) at low physiological concentrations. Activation of the soluble guanylyl cyclase by endogenous NO and the consequent increase in the second messenger cyclic GMP are now known to control a variety of biological functions. Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is inhibited by NO. However, it is not clear whether NO produced by the constitutive NO synthase interacts with cytochrome c oxidase, nor is it known what the biological consequences of such an interaction might be. We now show that NO generated by vascular endothelial cells under basal and stimulated conditions modulates the respiration of these cells in response to acute changes in oxygen concentration. This action occurs at the cytochrome c oxidase and depends on influx of calcium. Thus, NO plays a physiological role in adjusting the capacity of this enzyme to use oxygen, allowing endothelial cells to adapt to acute changes in their environment.

Original languageEnglish
Pages (from-to)1559-1562
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - Feb 16 1999

ASJC Scopus subject areas

  • Genetics
  • General

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