Purpose: Pulmonary arterial hypertension (PAH) is a disorder characterized by elevated pulmonary arterial pressure which leads to cardiac hypertrophy and dysfunction. Current treatments have marginal impact and additional therapies are required. Melatonin is a natural product shown to be cardioprotective against hypertension and myocardial ischemia. We propose that melatonin treatment may be cardioprotective in a model of monocrotaline (MCT) induced PAH.
Methods: Male Long Evans rats (150-175g) were injected with MCT (80mg/kg) which induced PAH after 28 days. Melatonin (6mg/kg) was added in drinking water after 14 days of PAH development, until day 28 (n>5). Cardiac hypertrophy was confirmed with a ratio of the right ventricle weight over left ventricle plus septal weight (RVW/LV+S). Cardiac functional parameters were assessed at day 28, using isolated heart perfusion and echocardiography including right ventricular systolic (RVSP), developed pressure (RVDP) and left ventricular end diastolic volume (LVEDV). We also assessed plasma levels of oxidative stress (TBARS).
Results: Melatonin reduced RVW/LV+S (0.56 ± 0.03 vs. 0.34 ± 0.03, p < 0.0006), RVSP (92.74 ± 5.13 mmHg vs. 79.82 ± 0.51mmHg, p < 0.0001) and RVDP (81.22 ± 2.75mmHg vs. 71.39 ± 0.57mmHg, p < 0.025). Melatonin also improved LVEDV (0.173 ± 0.01mL vs. 0.65± 0.08mL, p< 0.0002) and plasma TBARS (2.07 ± 0.28μM/mg protein vs. 1.25 ± 0.06μM/mg protein, p< 0.019).
Conclusions: Our data suggest that melatonin improves cardiac function in far progressed experimental PAH by decreasing oxidative stress. Melatonin may represent a novel therapeutic approach in the treatment of PAH.