Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

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 mu M increased permeability, while concentrations from 50 mu M to 5 mM reduced it. 3. The H-2 receptor antagonist cimetidine (2 mu M) blocked the effects of lower concentrations of histamine, while the H-1 receptor antagonist mepyramine (3 nM) blocked those of higher concentrations of histamine. 4. The effects of lower doses of histamine were mimicked by the H-2 receptor agonist dimaprit, and the effects of higher doses of histamine were mimicked by the H-1 receptor agonist alpha-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.