VASOACTIVE DRUGS INHIBIT OXYGEN RADICAL PRODUCTION OF NEUTROPHILS

A concentration response study was performed to clarify whether vasoac tive drugs, routinely used in intensive care patients, inhibit oxygen radical production of neutrophils. Moreover, in a cell-free system, it was investigated whether these drugs exert free radical scavenging pr operties. Vasoactive agents were incubated with neutrophils from healt hy human volunteers, which were stimulated by N-formyl-methionyl-leucy l-phenylalanine (FMLP) and by opsonized zymosan to produce oxygen radi cals, detected by chemiluminescence measurements. Sympathomimetics (ep inephrine greater than norepinephrine, dopamine and dobutamine) as wel l as phosphodiesterase-inhibitors (amrinone and enoximone) inhibited F MLP-induced and zymosan-induced oxygen radical production of neutrophi ls in a concentration-dependent and drug-specific fashion. With the ex ception of amrinone, FMLP-induced chemiluminescence of neutrophils was impaired nearly 10-fold more markedly than zymosan-induced chemilumin escence. Glyceryl trinitrate, nifedipine and prostacyclin had no effec t on oxygen radical production of neutrophils. In the cell-free system , epinephrine, norepinephrine, dopamine, amrinone and enoximone demons trated oxygen free radical scavenging properties. This study shows tha t vasoactive drugs, frequently used in the clinical setting, may suppr ess oxidative burst after FMLP-receptor stimulation. As demonstrated i n the cell-free system, this suppression was, at least in part, due to oxygen radical scavenging.