- 1The permeability response to acutely applied bradykinin and [des-Arg9]-bradykinin on single cerebral venular capillaries has been investigated using the low molecular mass fluorescent dyes Lucifer Yellow and Sulforhodamine B with the single vessel occlusion technique.
- 2When bradykinin was applied repeatedly for up to 2 h, the permeability increase was small and reversible for concentrations that ranged from 5 nm to 50 μm.
- 3The logEC50 of the permeability response to bradykinin was −5.3 ± 0.15 (logm; mean ±s.e.m.). This was reduced to −6.37 ± 0.24 with the angiotensin-converting enzyme inhibitor captopril, to −6.33 ± 0.19 with the neutral endopeptidase inhibitor phosphoramidon and to −7.3 ± 0.20 with captopril and phosphoramidon combined.
- 4The permeability response to bradykinin was blocked by the bradykinin B2 receptor antagonist HOE 140, by inhibition of the Ca2+-independent phospholipase A2, by the scavenging of free radicals, or by inhibition of both cyclo-oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SKF 96365 had no effect on the response.
- 5Application of [des-Arg9]-bradykinin also increased permeability over the concentration range 5 nm to 50 μm, with a logEC50 of −5.6 ± 0.37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H2 receptor blocker cimetidine.
- 6These results imply that the acute permeability response to bradykinin is mediated via the release of arachidonic acid, which is acted on by cyclo-oxygenase and lipoxygenase resulting in the formation of free radicals, and that the response to [des-Arg9]-bradykinin is mediated via histamine.