INCREASED NITRIC-OXIDE DEACTIVATION BY POLYMORPHONUCLEAR LEUKOCYTES IN PATIENTS WITH INTERMITTENT CLAUDICATION

Purpose: Local activation of polymorphonuclear leukocytes (PMNLs) is c onsidered an important aspect of the pathogenesis of intermittent clau dication, although concrete mechanisms of their effects an circulatory homeostasis in peripheral atherosclerotic disease remain unclear. Thi s study evaluated the ability of PMNLs to deactivate nitric oxide (NO) , a key regulator of regional circulation, as a possible factor determ ining PMNL involvement into ischemic disorders in patients who have in termittent claudication before and after vascular reconstruction. Meth ods: A total of 57 patients who had peripheral occlusive disease in an aortofemoral segment before surgical treatment (group 1) and 65 patie nts who had similar occlusive lesions and other clinical and demograph ic data 6 to 12 months after undergoing inflow vascular reconstruction (group 2) were examined. All patients from group 2 had anatomically p atent grafts; their satisfaction and level of function after surgical treatment were assessed by a five-point questionnaire. The sex- and ag e-matched control group included 35 subjects. NO activity was bioassay ed by measuring its ability to increase cyclic guanosine monophosphate (cGMP) accumulation in rat fetal lung-cultured fibroblasts (RFL-6 cel ls). The ability of PMNLs to deactivate NO was characterized as the pe rcent decrease in NO-induced cGMP accumulation in RFL-6 cells. Results : Stimulated PMNLs caused inhibition of the activity of authentic NO; accumulation of cGMP induced by sodium nitroprusside mas not affected. PMNLs from patients with peripheral atherosclerotic disease either be fore or after vascular reconstruction had a more marked capacity of NO inactivating than the cells from healthy subjects. For both groups of patients, levels of PMNL-induced NO deactivation were higher for pati ents with diabetes, and especially both diabetes and arterial hyperten sion. For both groups of patients, there was no correlation between le vels of PMNL-induced NO deactivation and resting ankle-brachial indexe s (ABIs). In contrast, close correlation was revealed between levels o f PMNL-induced NO deactivation and postexercise ABIs and percent decre ase in resting ABIs after exercise in patients evaluated either before or after surgical treatment. Conclusions: The ability of stimulated P MNLs to deactivate NO is elevated in peripheral occlusive disease and may be implicated in the pathogenesis of intermittent claudication. In patients who underwent successful recanalization of magistral arterie s, levels of PMNL-induced NO deactivation remained higher than in cont rol subjects. The increase in the ability of PMNL to deactivate NO pos itively correlated to ABI decreases after exercise in patients with pe ripheral occlusive disease either before or after surgical treatment.