Vasoconstriction in response to activated leukocytes: implications for vasospasm.

Three sets of experiments are presented demonstrating that activated leukocytes produce significant vasoconstriction. (1) Responses to human mononuclear leukocytes were studied in intact femoral arteries in vitro. Vasoconstriction of about 35-40% of the maximal effect obtained with KCl was found with mononuclear cells activated by thrombin or complement component C5a, but not with unactivated mononuclear cells. This vasoconstriction was endothelium-independent, and could not be inhibited by radical scavengers or by pre-treatment of the cells with inhibitors of the cyclooxygenase or lipoxygenase pathway. Additional experiments suggest that this contractile effect is partially mediated by the release of a stable factor. (2) Vascular responses to intra-arterial complement C5a (10 and 100 micrograms) were studied in the blood-perfused hind limb of normal and atherosclerotic monkeys in vivo. C5a injection produced pronounced constriction of the hind limb large arteries in atherosclerotic, but not in normal animals. Perfusion of the hind limb with a cell-free blood substitute almost abolished C5a-induced vasoconstriction. These findings suggest that C5a induces vasoconstriction by activation of blood cells, probably leukocytes. (3) Vascular responses to the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), were studied in the human coronary circulation. Intracoronary fMLP (1 x 10(-8) moles) produced a transient increase in blood flow velocity and a significant decrease of the diameter of the epicardial arteries. This effect was accompanied by a decrease in leukocyte count in the coronary sinus blood. These studies suggest that activated leukocytes produce vasoconstriction by the release of vasoactive factor(s), and thus may contribute to the pathogenesis of cardiovascular complications in patients with atherosclerosis.