Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries.
To assess how polymorphonuclear leukocytes (PMNs) act on coronary vasoactivity, we measured the changes in isometric tension of isolated rings of canine coronary arteries upon addition of autologous PMNs to organ chambers in which the rings were suspended. When PMNs isolated by the colloidal polyvinylpyrrolidone-coated silica (Percoll) gradient method were added to the chambers, ring preparations of left circumflex coronary arteries developed isometric tension. The increase in tension was dependent on the amount of PMNs (1 X 10(4) to 5 X 10(6) cells/ml). Maximal tension obtained by an optimal amount of PMNs (5 X 10(5) cells/ml) was almost comparable to that produced by prostaglandin F2 alpha (5 microM). Integrity of endothelial cells was not disrupted after the addition of PMNs because the developed tension could be reversed by the addition of acetylcholine in an endothelium-dependent manner. Mechanical rubbing of endothelium abolished the PMN-induced vasoconstriction, which was regained by placing an endothelium-unrubbed ring inside a rubbed ring ("sandwich preparation"). When PMN suspensions were pretreated with 5-lipoxygenase inhibitors of arachidonate, PMN-induced vasoconstriction was greatly suppressed, although the pretreatment of vascular preparations did not alter the development of isometric tension. These findings indicate that PMNs induce the contraction of coronary arterial rings in the presence of intact endothelial cells. The mechanism by which PMNs induce the contraction is the release of vasoconstrictive substances by metabolic interaction between PMNs and endothelial cells. Vasoconstrictive substances produced by the PMN-endothelial system, such as 5-lipoxygenase metabolites through a "leukotriene A4 steal" mechanism, may contribute to the contraction of vascular smooth muscle.