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Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

M. H. Sarker, A. S. Easton and P. A. Fraser

1. The permeability response of slightly leaky pial venular capillaries to histamine was investigated using the single microvessel occlusion technique.

2. Histamine dose-response curves showed that concentrations between 5 nm and 5 µM increased permeability, while concentrations from 50 µM to 5 mM reduced it.

3. The 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.

4. The 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 -2-(2-aminoethyl)pyridine (AEP).

5. Low concentrations of histamine, which normally increase the permeability of Lucifer Yellow (P_LY), 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.

6. The 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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