Fig. 3: Inhibition of RyR2 confers similar protective effect as RyR2 KO in CH-induced PH.

a Determination of RyRs activity by [³H]-ryanodine binding assays are conducted from PAs from TTC treatment group (n = 5 independent studies, 5 mice per study). b Summary of elevated PASMC resting [Ca²⁺]_i level after exposure to 3 weeks CH in administration of TTC. PASMC are loaded with fura-2/AM (5 µM) (n = 5 independent studies, 60 cells per study). c Bar graph summary of medium (3 mM) and maximal (30 mM) dosage of caffeine (Caf) -induced Ca²⁺ peak in TTC treatment group (n = 5 independent studies, 60 cells per study). d Pulmonary arterial contractility measured by concentration-response curve induced by norepinephrine, which obtained from TTC treated PA strips (n = 4 independent studies, 6 PA strips per study). e Typical lung sections of PAs from WT mice administrated by TTC (bar scale: 50 µm). Proportion of non-(Non), partially (Par), or fully (Mus) muscularized PAs in total counted PAs (n = 5 independent studies, 60 vessels per study). f Medial wall thickness of PAs sized 15–50, 51–100, and over 100 μm in relation to cross-sectional diameter (n = 5 independent studies, 60 vessels per study). PASMC proliferation (Ki-67 staining) in vivo after 3 weeks hypoxic condition (n = 5–7, 50–60 vessels per group). g Summarized the effect of CH or Nor on RVSP in saline (control) and tetracaine (TTC, 2 mg/kg/d) treatment group mice model, measured by 1.2F catheter. RV/LV + S to measure RV hypertrophy (n = 6 independent studies, 5 mice per study). Data are expressed as mean ± standard error. (*P < 0.05, using one-way ANOVA test).