ATRIAL-NATRIURETIC-PEPTIDE INHIBITS NITRIC-OXIDE SYNTHESIS IN MOUSE MACROPHAGES

The atrial natriuretic peptide (ANP) affects cardiovascular physiology , and, as has been suggested more recently, exerts immunomodulatory ac tivities. In this context, we examined the effect of ANP on nitric oxi de (NO) synthesis in murine bone marrow derived macrophages as well as in peritoneal macrophages. Cultured macrophages were stimulated with lipopolysaccharides (LPS 0.1-10 mu g/ml) and NO synthesis was monitore d by measuring increased concentrations of NO2 in the medium. In initi al experiments employment of N-G-monomethyl-L-arginine (L-NMMA) and de xamethasone, two specific inhibitors of nitric oxide synthase (NOS), c onfirmed the presence of inducible NOS activity in the cells. Exposure of cells to rat ANP99-126 in the range of 10(-8) to 10(-6) M signific antly decreased LPS induced NO synthesis over 24 hours of incubation. Thus, ANP may alter macrophage function by affecting their nitric oxid e synthesizing pathway.