Journal of Comparative Physiology B

, Volume 185, Issue 2, pp 153–171 | Cite as

The evolution of nitric oxide signalling in vertebrate blood vessels

  • John A. Donald
  • Leonard G. Forgan
  • Melissa S. Cameron


Nitric oxide is one of the most important signalling molecules involved in the regulation of physiological function. It first came to prominence when it was discovered that the vascular endothelium of mammals synthesises and releases nitric oxide (NO) to mediate a potent vasodilation. Subsequently, it was shown that NO is synthesised in the endothelium by a specific isoform of nitric oxide synthase (NOS) called NOS3. Following this discovery, it was assumed that an endothelial NO/NOS3 system would be present in all vertebrate blood vessels. This review will discuss the latest genomic, anatomical and physiological evidence which demonstrates that an endothelial NO/NOS3 signalling is not ubiquitous in non-mammalian vertebrates, and that there have been key evolutionary steps that have led to the endothelial NO signalling system being a regulatory system found only in reptiles, birds and mammals. Furthermore, the emerging role of nitrite as an endocrine source of NO for vascular regulation is discussed.


Nitric oxide Nitric oxide synthase Vertebrate Nitrite Endothelium Vasodilation 





Guanosine 3′:5′-cyclic monophosphate


Endothelium-derived hyperpolarisation


Endothelium-derived relaxing factor


Electron transport chain


Guanylyl cyclase


Guanosine triphosphate








Nicotinamide adenine dinucleotide phosphate


N 5-[imino(nitroamino)methyl]-l-ornithine methyl ester monohydrochloride


Nitric oxide


Nitric oxide synthase




Post synaptic density protein (PSD95)/drosophila disc large tumour suppressor protein/zona occludens-1 protein domain


Reactive oxygen species




Sodium nitroprusside


Whole genome duplication

Supplementary material

360_2014_877_MOESM1_ESM.pdf (290 kb)
Supplementary material 1 (PDF 290 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • John A. Donald
    • 1
  • Leonard G. Forgan
    • 1
  • Melissa S. Cameron
    • 1
  1. 1.School of Life and Environmental SciencesDeakin UniversityGeelongAustralia

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