Modulation of neutrophil migration and superoxide anion release by metoprolol

In addition to having anti sympathotonic effects, beta-blockers are thought to have some adrenoceptor-independent properties. Such ancilliary effects are described for carvedilol acting as oxygen radical scavenger and for pro pranolol which blocks protein kinase C and phosphatidate phosphohydrolase, The goal of our in vitro experiments was to identify ancilliary effects of the widely used beta-blockers metoprolol and atenolol in neutrophils. Neutr ophil chemotaxis was tested using the leading front assay in a modified Boy den microchemotaxis chamber. Respiratory burst activity was detected fluoro metrically. Inhibition of protein kinase C activity was tested with purifie d alpha-, beta- and gamma-isoenzyme preparation. Metoprolol dose-dependentl y inhibited formyl peptide-stimulated neutrophil chemotaxis and formylpepti de- and phorbol myristate acetate-triggered oxygen free radical production. These actions were not affected by the competitive presence of the beta-re ceptor agonist, orciprenaline. Effects of metoprolol, as well as of propran olol, and the signaling enzyme blockers were strongly time dependent. Propr anolol mimicked effects of staurosporine on respiratory burst, whereas the effects of metoprolol were similar to bisindolylmaleimide, a specific prote in kinase C blocker. Atenolol, a hydrophilic beta-blocker, neither affected neutrophil chemotaxis nor respiratory burst. In a cell-free system, metopr olol did not interfere with the activity of the purified protein kinase C a lpha-, beta- and gamma-isoenzymes. Adrenoceptor-independent inhibition of n eutrophil chemotaxis and free radical production is a novel mode of action of metoprolol that may be relevant for beneficial effects ot the beta-block er in heart failure and endothelial preconditioning. (C) 2000 Academic Pres s.