Vasomotor and permeability effects of bradykinin in the cerebral microcirculation

All components of an intracerebral kallikrein-kinin system have been described. Thus, bradykinin (BK) acting from the parenchymal site as well as from the blood site may influence cerebral microcirculation. BK is a potent dilator of extra- and intraparenchymal cerebral arteries when acting from the perivascular site. The vasomotor effect of BK is mediated by B-2 receptors which appear to be located at the abluminal membrane of the endothelial cell. The effect of BK is mediated by NO, prostanoids, free radicals, H2O2 or leukotrienes depending on the animal species and on the location of the artery. Selective opening of the blood-brain barrier for small tracers (Na+-fluorescein; MW, 376) has been found in cats during cortical superfusion or intraarterial application of BK. This leakage is mediated by B-2 receptors located at the luminal and abluminal membrane of the endothelial cells. Formation of brain edema has been found after ventriculo-cisternal perfusion or interstitial 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 concentrations which induce extravasation, dilatation and oedema formation has been found under several pathological conditions, Thus, BK may be involved in oedema formation after cold lesion, concussive brain injury, traumatic spinal cord and ischemic brain injury. The mediator role of BK in brain edema is further supported by therapeutic results. Brain swelling due to cold lesion or ischemia could be diminished by treatment with kallikrein-inhibitors. Similarly, dilatation of cerebral arterioles after concussive brain injury was reduced by blockade of B-2 receptors. Thus, all criteria favour BK as one mediator of vasogenic oedema.