VASOMOTOR AND PERMEABILITY EFFECTS OF BRADYKININ IN THE CEREBRAL MICROCIRCULATION

All components of an intracerebral kallikrein-kinin system have been d escribed. Thus, bradykinin (BK) acting from the parenchymal site as we ll as from the blood site may influence cerebral microcirculation. BK is a potent dilator of extra- and intraparenchymal cerebral arteries w hen acting from the perivascular site. The vasomotor effect of BK is m ediated by B-2 receptors which appear to be located at the abluminal m embrane of the endothelial cell. The effect of BK is mediated by NO, p rostanoids, free radicals, H2O2 or leukotrienes depending on the anima l species and on the location of the artery. Selective opening of the blood-brain barrier for small tracers (Na+-fluorescein; MW, 376) has b een found in cats during cortical superfusion or intraarterial applica tion of BK. This leakage is mediated by B-2 receptors located at the l uminal and abluminal membrane of the endothelial cells. Formation of b rain edema has been found after ventriculo-cisternal perfusion or inte rstitial infusion of BK. This can be explained by increase of vascular permeability and cerebral blood flow due to arterial dilatation thus enhancing driving forces for the extravasation. An increase of the BK concentration in the interstitial space of the brain up to concentrati ons which induce extravasation, dilatation and oedema formation has be en found under several pathological conditions, Thus, BK may be involv ed in oedema formation after cold lesion, concussive brain injury, tra umatic spinal cord and ischemic brain injury. The mediator role of BK in brain edema is further supported by therapeutic results. Brain swel ling due to cold lesion or ischemia could be diminished by treatment w ith kallikrein-inhibitors. Similarly, dilatation of cerebral arteriole s after concussive brain injury was reduced by blockade of B-2 recepto rs. Thus, all criteria favour BK as one mediator of vasogenic oedema.