The kallikrein-kinin system as mediator in vasogenic brain edema. Part 1: Cerebral exposure to bradykinin and plasma.

Plasma and bradykinin were perfused into the ventricular system of mongrel dogs to investigate whether either or both induce brain edema. Formation of cerebral edema was determined by measurement of cerebral water and electrolytes in periventricular white matter, cerebral cortex, and caudate nucleus. The response of cerebral tissue to exposure to bradykinin or to plasma, as a carrier of kininogens, was analyzed by assessment of the perfusate composition after ventricle passage. The authors report that cerebral administration of bradykinin induces cerebral edema. Ventricular perfusion with plasma also led to an increase of cerebral water content which was restricted to the white matter, but involved all brain tissue areas, if bradykinin was used. Ventricular perfusion with plasma was associated with consumption of the kinin precursor (kininogens) indicative of formation of kinins. Significant consumption of the precursor was found in five out of nine animals subjected to plasma perfusion of the ventricular system. In these animals a close correlation between the increase of white matter water content and kininogen-consumption as a measure of kinin-formation was obtained. Marked kinin-degrading activity was observed during ventricular perfusion with bradykinin as concluded from a considerable decrease of bradykinin concentration in the cisternal effluent compared to the inflowing perfusate concentration. Ventricular perfusion with plasma was associated with a decrease of K+ clearance capacity with continued duration, and in two animals with a release of glutamate into the plasma perfusate, suggesting an involvement of cytotoxic mechanisms. These findings provide support for the hypothesis of a mediator function of the kallikrein-kinin (KK) system in vasogenic brain edema. The next question that needs to be answered to complete the picture--does spontaneous activation of the KK system occur in conditions leading to vasogenic edema?--is studied in a subsequent report.