Table 1.
Baseline and post-treatment characteristics of the studied groups.
Figure 1.
Effects of riociguat and sildenafil on hemodynamics in SUHx rats.
(A) RVSP, (B) SAP, (C) CO and (D) TPR of different treatment groups. *p<0.05. Note. CO, cardiac output; RVSP, right ventricular systolic pressure; SAP, systemic arterial pressure; TPR, total pulmonary resistance.
Figure 2.
Effects of riociguat and sildenafil on RVH and fibrosis in SUHx rats.
(A) Ratio of the RV to LV+S and (B) RV collagen contents of different treatment groups. *p<0.05. Note. LV, left ventricle; RV, right ventricle; RVH, right ventricular hypertrophy; S, interventricular septum.
Figure 3.
Effects of riociguat and sildenafil on pulmonary vascular remodeling in SUHx rats.
(A) Proportion of non-, partially or fully muscularized pulmonary arteries as a percentage of the total pulmonary artery cross section (<50 µm); (B) proportion of medial wall thickness of the small pulmonary arteries (<50 µm); (C) proportion of opened, partly closed and closed small pulmonary arteries (<50 µm) and (D) neointima/media ratio of the small pulmonary arteries (<50 µm) of different treatment groups. *p<0.05. Note. c, closed; F, fully muscularized; N, non-muscularized; o, opened; P, partially muscularized; pc, partly closed.
Figure 4.
Localization of sGCα1, sGCβ1, eNOS and PDE-5 in pulmonary vessels of SUHx rats.
Localization of sGCα1, sGCβ1, eNOS and PDE-5 are presented in healthy controls, SUHx 3-week control animals and vehicle-treated animals. Note. eNOS, endothelial nitric oxide synthase; PDE-5, phosphodiesterase type 5; sGCα1, soluble guanylate cyclase α1; sGCβ1, soluble guanylate cyclase β1.
Figure 5.
Effects of riociguat and sildenafil on apoptosis and cell proliferation in the lung tissue of SUHx rats.
(A) Western blotting of caspase-3 and cleaved caspase-3 with densitometric analysis and (B) PCNA immunostaining with representative examples of different treatment groups. *p<0.05. Note. PCNA, proliferating cell nuclear antigen.
Figure 6.
Effects of riociguat and sildenafil on sGC and eNOS protein levels, and cGMP concentration in the lung tissue of SUHx rats.
(A) Western blotting of eNOS, sGCα1 and sGCβ1, (B) densitometric analysis of sGCα1/β-actin, (C) densitometric analysis of sGCβ1/β-actin, (D) densitometric analysis of eNOS/β-actin and (E) concentration of cGMP, in lung tissue of different treatment groups. *p<0.05. Note. eNOS, endothelial nitric oxide synthase; PDE-5, phosphodiesterase type 5; sGCα1, soluble guanylate cyclase α1; sGC, soluble guanylate cyclase; sGCβ1, soluble guanylate cyclase β1; cGMP, cyclic guanosine monophosphate.