Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta

Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by α(1)-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A(23187)-induced relaxations but also the catalase sensitive hydrogen peroxide (H(2)O(2)) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O(2) (•–)) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe(2)SO(4)/H(2)O(2)-produced hydroxyl radical ((•)OH) and H(2)O(2). Thus O(2) (•–) produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did (•)OH and H(2)O(2). In the large (conduit) artery, the effects of activated neutrophils and various ROS (O(2) (•–), (•)OH and H(2)O(2)) seem to be more dependent on muscle tension than on endothelial mechanisms.