We investigated the effect of C-reactive protein (CRP) and sodium azide (NaN(3)) on endothelial Cx43 gap junctions. Human aortic endothelial cells (HAEC) were treated with (a) detoxified CRP, (b) detoxified dialyzed CRP, (c) detoxified dialyzed CRP plus NaN(3), (d) NaN(3), or (e) dialyzed NaN(3). The concentration of CRP in all preparations was fixed to 25 microg/ml and that of NaN(3) in the preparations of (c) to (e) was equivalent to that contained in the 25 microg/ml CRP purchased commercially. The results showed that both the expression of Cx43 protein and gap junctional communication function post-48-h incubation were reduced and inhibited by the detoxified CRP, NaN(3), or detoxified dialyzed CRP plus NaN(3), but not by the detoxified dialyzed CRP or dialyzed NaN(3). Reverse transcription-polymerase chain reaction analysis of cells treated for 72 h also showed a pattern of transcriptional regulation essentially the same as that for the proteins. We concluded that CRP does not have a significant effect on Cx43 gap junctions of HAEC, but NaN(3) inhibited the viability of cells and downregulate their junctions.