LEUKOCYTE-INDUCED ACUTE ENDOTHELIAL DYSFUNCTION IN MIDDLE CEREBRAL-ARTERY IN RABBITS - RESPONSE TO AGGREGATING PLATELETS

Background and Purpose Recent evidence suggests a possible role for le ukocytes in angiospastic reactions of large cerebral arteries. This st udy examined the effect of activation of endogenous circulating leukoc ytes on endothelium-dependent relaxation in the middle cerebral artery in rabbits. Methods Leukocytes were activated by rapid injection of e ither 40 mu g/kg phorbol 12-myristate 13-acetate, or 0.2 mg/kg N-formy l-methionyl-leucylphenylalanine into the left carotid artery. Control rabbits received an equal volume of vehicle. Concentration-dependent i sometric tension responses of the left and right middle cerebral arter y to the dilators acetylcholine, ADP, sodium nitroprusside, or calcium ionophore (A23187), as well as to aggregating platelets, were compare d in vitro in control animals and in animals killed 10 minutes after t he injection of leukocyte activators in normal and leukocyte-depleted rabbits. Results In the control animals there was no significant diffe rence in the reactivity of the left and right middle cerebral arteries . The injection of the leukocyte activators led to enhanced contractil e responses to aggregating platelets and a significant reduction in th e endothelium-dependent relaxation in response to acetylcholine, ADP, and A23187 in the left middle cerebral artery (the injected side), whe reas the effect of an endothelium-independent dilator sodium nitroprus side remained unchanged. In leukocyte-depleted rabbits the injection o f either of the leukocyte activators used did not induce significant c hanges in the reactivity of the left middle cerebral artery. Conclusio ns Intravascular leukocyte activation appears to induce an acute distu rbance of the endothelium-dependent relaxation. Under these conditions , platelet activation might result in marked angiospastic reactions of large cerebral arteries.