Nitric oxide enhances PGI2 production by human pulmonary artery smooth muscle cells

To evaluate the effect of exogenous nitric oxide (NO) and endogenous NO on the production of prostacyclin (PGl(2)) by cultured human pulmonary artery smooth muscle cells (HPASMC) treated with lipopolysaccharide (LPS), interleukin-1(beta) (IL-1(beta)), tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFNgamma), HPASMC were treated with LPS and cytokines together with or without sodium nitroprusside (SNP), NO donor, N-G-monomethyl-L-arginine (L-NMMA), NO synthetase inhibitor, and methylene blue (MeB), an inhibitor of the soluble guanylate cyclase. After incubation for 24 h, the postculture media were collected for the assay of nitrite by chemiluminescence method and the assay of PGl(2) by radioimmunoassay. The incubation of HPASMC with various concentrations of LPS, IL-1(beta) or TNFalpha for 24 h caused a significant increase in nitrite release and PGI, production. However, IFN gamma slightly increased the release of nitrite and had little effect on PGl(2) production. Although the incubation of these cells for 24 h with SNP did not cause a significant increase in PGl(2) production, the incubation of HPASMC with SNP and 10 mu g/ml LPS, or with SNP and 100 U/ml IL-1 beta further increase PGl(2) production and this enhancement was closely related to the concentration of SNP. However, stimulatory effect of SNP on PGl(2) production was not found inTNF(alpha)- and IFN gamma- treated HPASMC. Addition of L-NMMA to a medium containing LPS or IL-1(beta) reduced nitrite release and attenuated the stimulatory effect of those agents on PGl(2) production. MeB significantly suppressed the production of PGl(2) by HPASMC treated with or without LPS or IL-1(beta). The addition of SNP partly reversed the inhibitory effect of MeB on PGl(2) production by HPASMC. These experimental results suggest that NO might stimulate PGl(2) production by HPASMC. Exogenous NO together with endogenous NO induced by LPS or cytokines from smooth muscle cells might synergetically enhance PGl(2) production by these cells, possibly in clinical disorders such as sepsis and acute respiratory distress syndrome. (C) 2000 Harcourt Publishers Ltd.