Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries

Abstract

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. 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 × 106 ml−1. The contractile response was also found in endothelium‐denuded vascular rings. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (−)‐noradrenaline. At a cell number of 2.5 × 106 PMN ml−1 the pD2‐value for (−)‐noradrenaline was augmented 0.40 ± 0.05 (P < 0.001), while total contraction at the highest concentration (−)‐noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 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. 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 Fα in the supernatant. 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. 1992 British Pharmacological Society