Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries

1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-)-noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-)-noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-)-noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor.