Rutaecarpine attenuates monocrotaline-induced pulmonary arterial hypertension in a Sprague-Dawley rat model

Background: Pulmonary arterial hypertension presents with obliterative remodeling of the pulmonary arteries and progressive elevation of pulmonary vascular resistance, which increase the risk of right ventricular failure and death. It has been reported in previous studies that rutaecarpine plays a crucial role in anti-inflammatory and antioxidant activities, which may help regulate cell apoptosis and cell proliferation. The purpose of this study was to determine the effects of rutaecarpine in the rat model of monocrotaline-induced pulmonary hypertension. Methods: We induced pulmonary arterial hypertension in adult Sprague-Dawley rats by injecting monocrotaline (60 mg/kg) and then treated with rutaecarpine (40 mg/kg center dot d) or sildenafil (30 mg/kg center dot d) (positive control). Subsequently, pulmonary function, inflammation, cytokines and pulmonary vascular remodeling or proliferation were assessed. Results: Rutaecarpine was found to improve monocrotaline-induced mean pulmonary artery pressure, cardiac index, right heart index, right ventricular hypertrophy index, pulmonary artery remodeling and pulmonary function. reverse transcription-quantitative polymerase chain reaction demonstrated a decrease in tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta, whereas western blots a significantly decrease in the expression of nuclear factor kappa-B, endothelin-1, extracellular signal-regulated kinases 1/2, B cell lymphoma-2, Beclin1 and microtubule-associated protein1 light chain 3-II protein, and increase in the expression of Bax, caspase-3 and p62 protein. Conclusion: Rutaecarpine attenuated pulmonary arterial hypertension by inhibiting inflammation, oxidative stress, cell proliferation and autophagy, while promoting apoptosis.