INACTIVATION OF NITRIC-OXIDE BY POLYMORPH ONUCLEAR LEUKOCYTES AS A MECHANISM OF CIRCULATORY DISORDERS IN ATHEROSCLEROSIS

To investigate the mechanism by which polymorphonuclear leukocytes con tribute to circulatory disorders in atherosclerosis, we bioassayed nit ric oxide activity by measuring its ability to increaser cGMP accumula tion in cultured fibroblasts in the absence or presence of polymorphon uclear leukocytes from healthy volunteers and patients with atheroscle rosis. Nonactivated polymorphonuclear leukocytes did not alter NO-indu ced stimulation of cGMP accumulation in the detector cells. Activated polymorphonuclear leukocytes inhibited NO-induced cGMP accumulation wh ereas the effect of sodium nitroprusside was unaffected. Polymorphonuc lear leukocytes from patients with atherosclerosis impaired NO-depende nt cGMP accumulation more markedly than leukocytes from healthy volunt eers. In atherosclerotic patients polymorphonuclear leukocytes from bl ood taken from femoral artery distal to stenotic lesions destroyed nit ric oxide significantly higher than those taken from venous blood. It was assumed that inactivation of nitric oxide by activated polymorphon uclear leukocytes is one of mechanisms leading to regional circulatory disorders in atherosclerosis.