Acetylcholine‐induced relaxation in bovine isolated mesenteric arteries is suppressed by polymorphonuclear leukocytes

Abstract

The endothelium plays a critical role in maintaining vascular tone via generation of potent vasoconstrictor and dilator substances. We examined the effect of bovine purified polymorphonuclear leukocytes (PMN) on the endothelium‐dependent relaxation to acetylcholine in isolated mesenteric arteries. In the presence of PMN (2.5 × 106 cells ml−1) the maximal relaxation to acetylcholine was decreased from 76.1 ± 2.4% to 44.9 ± 7.4% of the precontraction (P < 0.001). This effect was inhibited by superoxide dismutase and NG‐mono‐methyl‐l‐arginine, but not by catalase or indomethacin. PMN were not able to influence significantly the endothelium‐independent relaxation to nitroprusside. Removal of PMN after preincubation and prior to precontraction and relaxation did not influence the acetylcholine‐induced relaxation, indicating that no irreversible vascular damage had occurred. Superoxide anion production by unstimulated PMN was less than 10% compared to phorbol myristate acetate‐activated PMN, measured by chemiluminescence and reduction of ferricytochrome c. We conclude that small amounts of superoxide anions produced by unstimulated PMN contribute to a decrease in relaxation to acetylcholine by interfering with endothelium‐derived nitric oxide. 1993 British Pharmacological Society