Effects of sildenafil and metformin on endothelin-1 in the progression of pulmonary hypertension
Abstract
BACKGROUND: Pulmonary hypertension (PH) is a progressive and potentially fatal condition if left untreated. Currently, only sildenafil and bosentan have been approved by the Food and Drug Administration for the medical treatment of pediatric patients. The availability of bosentan, in a developing country, such as Indonesia, is a challenge.
AIM: To evaluate the effect of sildenafil and metformin on endothelin (ET)-1 levels in the progression of PH.
METHODS: Forty-eight, 12-week-old, male Wistar rats, weighing 117-193 g, were injected by monocrotaline (MCT) [60 mg/kg body weight (BW)] subcutaneously. The rats were then randomly assigned to four groups (control, sildenafil, metformin, and sildenafil plus metformin). One day after MCT injection, sildenafil (5 mg/kg BW) and metformin (100 mg/kg BW) were administered once daily for 21 days. Right heart catheterization was performed on day 22 after anesthesia with ketamine 50 mg/kg BW and xylazine 5 mg/kg BW intramuscularly. Blood was taken intracardially for approximately 3.5 ml, and the rats were euthanized. The serum was stored in -20° refrigerator before ELISA analysis. The lung was harvested and paraffin-blocked for later histology analysis. Blood serum was analyzed for ET-1, and a section of paraffin-blocked lung was stained with hematoxylin-eosin and α-smooth muscle actin. Intima media thickness (IMT) of 50-200 µm artery and ratio of pulmonary artery (PA) smooth muscle cells/fibroblast were analyzed.
RESULTS: The mean PA…
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