Incubation of human proximal tubular cells with ANF or c(4-23)ANF dose-dependently stimulated nitric oxide production while paradoxically inhibiting cytokine activation of inducible nitric oxide synthase.
ANF modulates nitric oxide production in human proximal tubular cells via the NPR-C receptor, demonstrating both stimulatory and inhibitory effects depending on cytokine presence.
OBJECTIVES: To investigate the possible immunomodulatory and regulatory functions of atrial natriuretic factor (ANF) and the natriuretic peptide C (NPR-C) receptor in the control of cytokine-stimulated nitric oxide production in primary cultures of human proximal tubular cells. METHODS: Freshly prepared human proximal tubular cells were seeded on plastic plates and allowed to reach confluence. The confluent cells were then incubated with ANF or cyclic(4-23)ANF (c(4-23)ANF) alone, or preincubated with ANF or c(4-23)ANF before incubation with the nitric oxide-stimulating combination of cytokines interleukin-1 beta (10 u/ml), tumour necrosis factor-alpha (10 ng/ml) and interferon-gamma (100 u/ml). RESULTS: In the present series of experiments we have found that incubation of primary cultures of human proximal tubular cells with ANF or c(4-23)ANF stimulates nitric oxide production dose-dependently. Paradoxically, ANF acting via the NPR-C receptor also inhibits cytokine activation of the enzyme-inducible nitric oxide synthase via a cyclic GMP-independent mechanism. Both of these effects were reproduced by the NPR-C receptor-specific ligand c(4-23)ANF. CONCLUSIONS: These findings represent novel actions of ANF mediated via the NPR-C receptor. The results also provide a simple model system in which to study the subcellular mechanisms of NPR-C receptor activation.
McLay et al. (Thu,) conducted a other in In vitro study. Atrial natriuretic factor (ANF) or cyclic(4-23)ANF vs. Cytokines alone or baseline was evaluated on Nitric oxide production. Incubation of human proximal tubular cells with ANF or c(4-23)ANF dose-dependently stimulated nitric oxide production while paradoxically inhibiting cytokine activation of inducible nitric oxide synthase.