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Downsides to the nitrate–nitrite–nitric oxide pathway in physiology and therapeutics?

Nature Reviews Drug Discovery volume 7, page 710 (2008)Cite this article

In their recent Review article (The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Rev. Drug Discov. 7, 156–167 (2008))1, Lundberg and colleagues describe the concept of the nitrate–nitrite–nitric oxide (NO) pathway in physiology and therapeutics. However, there are some issues that merit consideration with regard to its physiological and pharmacological significance.

First, the authors are proponents of nitrite as an NO donor under severe hypoxic conditions, and according to Ref. 1, this mechanism, as mediated by deoxyhaemoglobin, should operate maximally at 50% haemoglobin saturation (P50). However, although this state may exist momentarily in metabolically active tissues such as the heart, it must be appreciated that the pulmonary venous haemoglobin saturation is usually around 75% (pO2 ≈ 40 mm Hg).

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References

  1. Lundberg, J. O., Weitzberg, E. & Gladwin, M. T. The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Rev. Drug Discov. 7, 156–167 (2008).

    Article  CAS  Google Scholar 

  2. Millar, T. M. et al. Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Lett. 427, 225–228 (1998).

    Article  CAS  Google Scholar 

  3. Cosby, K. et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nature Med. 9, 1498–1505 (2003).

    Article  CAS  Google Scholar 

  4. Panesar, N. S. Role of chloride and inhibitory action of inorganic nitrate on gonadotropin-stimulated steroidogenesis in mouse Leydig tumor cells. Metabolism 48, 693–700 (1999).

    Article  CAS  Google Scholar 

  5. Panesar, N. S. & Chan, K. W. Decreased steroid hormone synthesis from inorganic nitrite and nitrate. Studies in vitro and in vivo. Toxicol. Appl. Pharmacol. 169, 222–230 (2000).

    Article  CAS  Google Scholar 

  6. Hodge, L. Environmental Pollution (Holt, Rinehart and Winston, New York, 1973).

    Google Scholar 

  7. MacArthur, P. H., Shiva, S. & Gladwin, M. T. Measurement of circulating nitrite and S-nitrosothiols by reductive chemiluminescence. J. Chromatogr. B 851, 93–105 (2007).

    Article  CAS  Google Scholar 

  8. Pelley, J. Nitrate eyed as endocrine disrupter. Environ. Sci. Tech. 37, 162A (2003).

    Article  Google Scholar 

  9. White, P. C., New, M. I. & Dupont B. Congenital adrenal hyperplasia. N. Engl. J. Med. 316, 1519–1524 (1987).

    Article  CAS  Google Scholar 

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  1. is at the Department of Chemical Pathology, Nirmal Singh Panesar, Ph.D., The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. nspanesar@cuhk.edu.hk,

    Nirmal Singh Panesar

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  1. Nirmal Singh Panesar
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Panesar, N. Downsides to the nitrate–nitrite–nitric oxide pathway in physiology and therapeutics?. Nat Rev Drug Discov 7, 710 (2008). https://doi.org/10.1038/nrd2466-c1

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