Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension
Abstract
BACKGROUND: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH). METHODS: A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments. RESULTS: Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1β…
Read the paper
Related studies
- Drug repositioning: a brief overview
- Cyclic nucleotide phosphodiesterases in Drosophila melanogaster
- Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
- Current View on Green Tea Catechins Formulations, Their Interactions with Selected Drugs, and Prospective Applications for Various Health Conditions
- In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease
- Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.