Table 2.
The treatment effects of aldosterone-Raptor inhibition on pulmonary hypertension in MCT-PAH in vivo
| Variable | Control | MCT |
P | |||
|---|---|---|---|---|---|---|
| Untreated | si-Scc | si-Raptor | si-Raptor + Sp | |||
| Weight (g) | 251 (8.2) | 295 (34.4)* | 307 (8.1)* | 292 (8.5)* | 291 (8.5)* | < 0.0001 |
| HR (bpm) | 276 (8.6) | 271 (8.7) | 260 (7.6) | 288 (5.0) | 279 (7.8) | 0.10 |
| RAP (mmHg) | 4.1 (0.8) | 6.5 (1.3) | 7.5 (0.9)* | 6.2 (0.2) | 4.9 (0.4) | < 0.05 |
| PASP (mmHg) | 26 (1.9) | 77 (5.2)* | 47 (2.0)*,** | 46 (2.5)*,** | 38 (1.7)*,**,† | < 0.0001 |
| MAP (mmHg) | 79 (4.5) | 68 (3.6) | 72 (6.5) | 78 (6.9) | 86 (5.4) | 0.23 |
| LVEDP (mmHg) | 8.5 (0.6) | 10.4 (0.5) | 7.3 (1.6) | 10.0 (0.9) | 9.0 (1.3) | 0.36 |
| CI (L/min/g) | 218 (10.2) | 147 (5.3)* | 115 (16.6)* | 213 (15) | 210 (7.2) | < 0.0001 |
| PVRi (mmHg⋅min⋅g/ml) | 32 (3.4) | 70 (13.1)* | 82 (6)*,** | 26 (7.6)** | 24 (3.9)** | < 0.0001 |
| RV/LV + S | 0.24 (0.02) | 0.38 (0.09)* | 0.33 (0.07)* | 0.25 (0.04)** | 0.24 (0.05)** | < 0.0001 |
In a disease prevention experimental design, male Sprague-Dawley rats were injected with vehicle control (n = 4 rats/condition) or MCT (50 mg/kg) and treated with Staramine-mPEG (2 mg/kg i.v.; 4 total doses/rat) formulated with si-Scc, si-Raptor, or si-Raptor plus spironolactone (SP; 25 mg/kg/d; n = 6–7 rats/condition), and at days 21–23 hemodynamics were assessed by cardiac catheterization. HR, heart rate; LVEDP, LV end-diastolic pressure; LV + S, left ventricle + septum; MAP, mean arterial pressure; RAP, right atrial pressure. P values indicate results from 1-way ANOVA. Post hoc analyses using the Tukey method indicated the following: *P < 0.05 vs. control; **P < 0.05 vs. MCT; †P < 0.05 vs. MCT + si-Raptor. Data are presented as mean (sem). RV/LV + S ratio of weight is given in grams.