Substance P increases microvascular permeability via nitric oxide-mediated convective pathways

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Abstract

The goal of these studies was to examine the effects of substance P, a tachykinin neuropeptide, on pathways of microvascular permeability. Individual frog mesenteric venular capillaries were cannulated, and albumin apparent permeability coefficients (P(s)) were determined by quantitative fluorescence microscopy. P(s) of albumin (P(sAlb)) rose from 6.8 ± 1.8 (SE) cm · s-1 · 107 at control to 22.3 ± 2.3 cm · s-1 · 107 when substance P (10-11 M) was perfused. The effect of increased microvessel permeability induced by substance P (10-11 M) was blocked with the nonpeptide substance P receptor antagonist CP-96,345 and N(G)-nitro-L- arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. P(sAlb) increased 0.99 cm · s-1 · 107 for every cmH2O increase in microvessel pressure after treatment of the vessel with substance P, demonstrating coupling of albumin flux to transvascular water flow. In conclusion, the mechanism of increased microvessel permeability in response to substance P appears to be the result of receptor-mediated increase in nitric oxide production and formation of water-filled convective pathways presumably located between adjacent endothelial cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume268
Issue number4 37-4
StatePublished - 1995

Keywords

  • albumin
  • endothelial cell-derived relaxing factor
  • macromolecule
  • neurokinin
  • nitric oxide synthase
  • permeability
  • quantitative fluorescence microscopy

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

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