Activation of monocyte constitutive nitric oxide synthase impairs adhesion to human saphenous vein

Morphine and endothelin-1 (ET-1) are endogenously produced vasoactive mediators that are released in response to tissue injury and have been demonstrated to trigger endothelium-dependent nitric oxide (NO) release. We evaluated the effects of morphine and ET-1 on human peripheral blood monocyte (PBM) NO release and adhesion. Treatment of PBM with morphine or ET-1 induced nanomolar release of NO within 2-5 min of agonist exposure followed by a rapid return to basal levels of production. Morphine and ET-1 induced NO release was abrogated by preincubation with the constitutive nitric oxide synthase (cNOS) inhibitor. L-NNA, whereas the inducible NOS (iNOS) selective inhibitor, aminoguanidine, was much less effective. Upregulation of iNOS by 24 hr preincubation with IFNγ, abrogated morphine and ET-1 but not ionomycin-induced NO release. Exposure of PBM adherent in fibronectin-coated slides to morphine or ET-1 induced a shift in cellular conformation from ameboid to round, whereas conformation al changes in IFNγ-stimulated PBM were markedly attenuated. Adhesion of PBM to human saphenous vein was markedly reduced by pretreatment with morphine or ET-1. Importantly, a marked decrease in cellular adhesion was observed well beyond the duration of NO release. These data suggest that NO release induced by morphine and ET-1 may require cNOS activation and may attenuate PBM adhesion at sites of injury.