Innervation and neurokinin receptors during angiogenesis in the rat sponge granuloma |
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Authors: | D A Walsh D -E Hu P I Mapp J M Polak D R Blake and T -P D Fan |
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Institution: | (1) Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ Cambridge, UK;(2) Inflammation Group, The London Hospital Medical College, Arthritis and Rheumatism Council Building, Whitechapel, E1 2AD London, UK;(3) Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, W12 0NN London, UK |
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Abstract: | Summary Angiogenesis is an essential component of wound healing and inflammation. In the rat subcutaneous sponge implantation model,
angiogenesis can be enhanced by administration of the sensory neuropeptide, substance P. We have used quantitativein vitro receptor autoradiography and immunohistochemistry to investigate the development of endogenous neurovascular regulatory systems
in the newly-formed granulation tissue of this model. The fraction of endothelial cells immunoreactive for proliferating cell
nuclear antigen, endothelial fractional area, and133Xe clearance were used as measures of endothelial proliferation, neovascularization, and blood flow, respectively. Endothelial
proliferation occurred predominantly in tissues surrounding the sponge, and peaked before neovascularization of sponge stroma
and the establishment of sponge blood flow. Substance P-containing sensory nerves and specific, high affinity substance P
binding sites with characteristics of neurokinin receptors of the NK1 subclass, were localized to microvessels surrounding the sponge at all time points. Lower density substance P binding sites
were localized to newly formed microvessels within the sponge stroma, progressively increasing in density from day 4 to day
14. Nerve fibres were observed in the stroma of only 2 of 6 sponges at day 14, and none at earlier time points. These data
support the hypothesis that substance P-enhanced angiogenesis in this model results from a direct action on microvascular
NK1 receptors. Neovascularization is a sequential process, with early endothelial proliferation followed by new vessel formation
and increased blood flow, with maturation of endogenous neurovascular regulatory systems occurring late in this process in
inflamed tissues. |
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