Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

Authors

  • M. H. Sarker,

    1. Vascular Biology Research Centre, Physiology Group, Biomedical Sciences Division, King's College London, Campden Hill Road, London W8 7AH, UK
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  • A. S. Easton,

    1. Vascular Biology Research Centre, Physiology Group, Biomedical Sciences Division, King's College London, Campden Hill Road, London W8 7AH, UK
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  • P. A. Fraser

    1. Vascular Biology Research Centre, Physiology Group, Biomedical Sciences Division, King's College London, Campden Hill Road, London W8 7AH, UK
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Corresponding author P. A. Fraser: Vascular Biology Research Centre, Physiology Group, Biomedical Sciences Division, King's College London, Campden Hill Road, London W8 7AH, UK. Email: paul.fraser@kcl.ac.uk

Abstract

  • 1The permeability response of slightly leaky pial venular capillaries to histamine was investigated using the single microvessel occlusion technique.
  • 2Histamine dose-response curves showed that concentrations between 5 nm and 5 μM increased permeability, while concentrations from 50 μM to 5 mM reduced it.
  • 3The H2 receptor antagonist cimetidine (2 μM) blocked the effects of lower concentrations of histamine, while the H1 receptor antagonist mepyramine (3 nM) blocked those of higher concentrations of histamine.
  • 4The effects of lower doses of histamine were mimicked by the H2 receptor agonist dimaprit, and the effects of higher doses of histamine were mimicked by the H1 receptor agonist α-2-(2-aminoethyl)pyridine (AEP).
  • 5Low concentrations of histamine, which normally increase the permeability of Lucifer Yellow (PLY), reduced it when co-applied with the phosphodiesterase 4 (PDE4) inhibitor rolipram. Rolipram also potentiated the response to AEP, but had no effect on that to dimaprit.
  • 6The effects of dimaprit were blocked by reducing extracellular Ca2+ from 2.5 mM to nominally Ca2+ free, or by applying the calcium entry blocker SKF 96365.

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