Melatonin improves adverse vascular remodelling and redox homeostasis in monocrotaline-induced pulmonary arterial hypertension.

Abstract

This study explored the effects of melatonin on cardiac and vascular function, and redox homeostasis in model PAH. Male Wistar rats were divided into: control (CTR), monocrotaline [MCT (60 mg/kg, single dose i.p)], monocrotaline + sildenafil [MCT + SIL (50 mg/kg/day)], and monocrotaline + melatonin [MCT + MEL (10 mg/kg/day)]. This protocol lasted 21 days. Echocardiographic, morphometric, histological, vascular reactivity, and oxidative/nitrosative stress analyses were performed. The reduced diastolic function and AT/ET ratio in the MCT group were partially attenuated by melatonin and sildenafil treatment (p < 0.05). Increased RV hypertrophy and pulmonary congestion were reduced by both treatments (p < 0.05). MCT-induced pulmonary arteriolar muscle layer hypertrophy was also reduced by both treatments (p < 0.05). MCT and MCT + SIL present diminished vasorelaxation as compared to control (p < 0.05). Augmented oxidative/nitrosative stress and reduced glutathione-s-transferase activity in MCT were mitigated by both treatments (p < 0.05). Then, melatonin was as effective as sildenafil against PAH-induced oxidative stress and pathological vascular remodelling.