Figure 2.

PKG does not mediate the downregulation of sGC protein and activity by chronic NO. When PPAECs were incubated for 72 h in the absence or presence of increasing concentrations of (A) the NO-independent sGC stimulator, YC-1 (N = 6), this did not cause downregulation of sGCα₁ and sGCβ₁ expression but rather a small upregulation. Consistent with this, in (B) the direct PKG activator 8-Br-cGMP (N = 6) led to increased sGCα₁ protein expression. (C) The scheme summarizes the in-vivo and in-vitro data suggesting that the downregulation of sGC protein and activity by chronic NO is cGMP- and PKG-independent and thus appeared to be due to a non-canonical mechanism. (D) sGC protein expression (N = 4) and (E) activity (N = 4) are not altered in PKG^−/− as compared to wildtype mice. Data are expressed as mean ± SEM. *,**,***p < 0.05, 0.01 or 0.001 vs. control, respectively. Representative full-length blots are presented in Supplementary Figure S4.