Intracellular accumulation of cAMP, but not cGMP, results in large inter-endothelial gap formation and increased endothelial permeability.
A, sGC α-wt/β-wt mutant cells induced with doxycycline and treated with 100 μm developed smaller inter-endothelial gaps (see also supplemental Movie 3). B, doxycycline induction and treatment with 100 μm sGC α-wt/β-wt mutant cells did not increase endothelial cell permeability as measured by macromolecular flux to a 40-kDa FITC-labeled dextran tracer. n = 7 independent experiments. C, sGC α-Q/β-KD mutant cells induced with doxycycline and treated with 100 μm SNP developed large inter-endothelial gaps over a 2-h time period (see also supplemental Movie 2). D, doxycycline induction and treatment with 100 μm SNP in sGC α-Q/β-KD mutant cells increased endothelial cell permeability as measured by macromolecular flux to a 40-kDa FITC-labeled dextran tracer. n = 8 independent experiments. One-way ANOVA was used to assess significance for each condition over the 120-min time course. Two-way ANOVA was used to make comparisons between treatments. *, p < 0.05 versus vehicle control; [caret], p < 0.05 versus base line.