RELAXATION OF DISTAL COLONIC CIRCULAR SMOOTH-MUSCLE BY NITRIC-OXIDE DERIVED FROM HUMAN-LEUKOCYTES

The role of nitric oxide (NO) as a mediator of colonic circular smooth muscle relaxation by human leucocytes was investigated. Granulocytes and mononuclear cells were obtained by gradient centrifugation of veno us blood from healthy volunteers. Both cell types relaxed precontracte d distal colonic circular smooth muscle in a concentration dependent m anner. Muscle relaxation was inhibited by preincubation of cells with N(G)-monomethyl-L-arginine (100 muM/l) but not by preincubation with N (G)-monomethyl-D-arginine (100 muM/1). Muscle relaxation by cells was reduced by 200 nM oxyhaemoglobin and 10 muM methylene blue but was inc reased by 60 units/ml superoxide dismutase. Non-viable cells did not p roduce muscle relaxation. Activation of mononuclear cells by incubatio n with 100 nM/l FMet-Leu-Phe increased muscle relaxation, whereas acti vation of granulocytes did not. Granulocytes and mononuclear cells rel ax precontracted distal colonic circular smooth muscle in vitro by the release of NO that may contribute to motility disorders of the gut as sociated with inflammation.