INHIBITION BY A STABLE FACTOR DERIVED FROM NEUTROPHILS OF ENDOTHELIUM-DEPENDENT RELAXATION IN RAT AORTA

Polymorphonuclear leukocytes (PMNs) may play an important role in many pathophysiological states. The effect of a factor derived from PMNs o n endothelium-dependent relaxation was studied using rat aortic rings in organ chambers. PMNs were obtained from cardiac surgical patients a nd healthy volunteers. After incubation in Krebs solution for 3 h, sup ernatants of PMN suspensions were isolated and used to pretreat the ao rtic rings for 30 min. The results showed that the supernatants derive d from 1 X 10(4) to 5 X 10(6) cells/ml PMNs produced a concentration-d ependent inhibition of endothelium-dependent relaxation to acetylcholi ne but not endothelium-independent relaxation to sodium nitroprusside. The effect could not be prevented by oxygen free radical scavenger su peroxide dismutase (150 U/ml), catalase (1,200 U/ml), or mannitol (20 mM) used alone or in combination. Heating the supernatants at 95-degre es-C for 30 min did not reduce the inhibitory effect. L-Arginine at 3 x 10(-5) to 3 x 10(-3) M did not significantly reverse the inhibitory effect of the PMN-derived factor. In conclusion, this study reveals th at a heat-stable factor derived from human PMNs potently inhibits acet ylcholine-induced endothelium-dependent relaxation but not sodium nitr oprusside-induced endothelium-independent relaxation in rat aorta. Thi s inhibitory effect is not caused by oxygen free radicals, a limitatio n of nitric oxide precursor or other unstable factors.