Antagonism of LPS and IFN-gamma induced iNOS expression in human atrial endothelia by morphine, anandamide, and estrogen

AIM: To determine whether inducible nitric oxide synthase (iNOS) stimulation of human atrial fragments can be diminished by the naturally occurring signal molecules, such as morphine, anandamide, and estrogen. The use of iNOS as an indicator is justified since it has been associated with initiation of various types of cellular damage either directly or indirectly. METHODS: Western blots were performed on control and drug-exposed atrial tissue before and after lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) exposure. RESULTS: Preincubation of the tissue with morphine, anandamide or estrogen prior to, but not after, the addition of LPS + IFN-gamma, blocked iNOS expression. The nitric oxide donor SNAP also blocked iNOS induction while preincubation of atrial fragments with an inhibitor of NOS, L-NAME, prior to morphine or anandamide exposure, restored LPS + IFN-gamma induction of iNOS. CONCLUSION: These data suggest a direct regulatory link at the transcriptional level between constitutive (c) NOS and iNOS in human atrial tissue.