sGC and cGMP in normal and fibrotic livers. (A) Sections of livers from vehicle (normal) and CCl4 (fibrotic) groups were stained with antibodies against sGCα1 and sGCβ1. Arrowheads denote fibrotic bridges. (Scale bar: 25 μm.) (B) mRNA levels for the sGCα1 and sGCβ1 genes. (C) Western blots for sGCβ1, α-SMA, and GAPDH were performed on liver lysate. (D) cGMP production in response to stimulation was measured in the control group (n = 8) and the CCl4-induced fibrosis group (n = 7). PBS (vehicle), praliciguat (PRL) (1 mg/mL), and SNP (S) (100 µM) plus praliciguat (1 mg/mL) were locally delivered by retrodialysis. (E) Levels of cGMP in the liver after 4 d of oral dosing with praliciguat (10 mg/kg) (n = 15) or vehicle (n = 10). Significance determined using an unpaired t test. ns, not significant; *P ≤ 0.05; **P ≤ 0.01; ****P ≤ 0.0001.