Agus Cahyono, Irwanto, Mahrus Abdur Rahman, Widjiati Widjiati
Universitas Airlangga. Universitas Surabaya.
Indonesia
Open Veterinary Journal
Open Vet J 2025; 15: 3087-3096
DOI: 10.5455/OVJ.2025.v15.i7.20
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 pressure (mPAP) and ET-1 of the treatment group were significantly lower than those of the control group. IMT was significantly lower in the sildenafil plus metformin group than in the other groups.
Conclusion: Sildenafil and metformin alone or in combination improve mPAP and ET-1 levels. Sildenafil plus metformin prevents artery remodeling in the PH model.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Animal Models of Pulmonary Vascular Disease and Therapy
Medical Therapy. Efficacy or Lack of Efficacy
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes