Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodeling, according to a new study in a rat model of pulmonary arterial hypertension (PAH) that was published in BMC Pulmonary Medicine. However, combining dapagliflozin with sildenafil was not more effective than sildenafil alone.
Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor. It can reduce cardiovascular events and mortality in patients with heart failure. Here, a team of researchers from China investigated whether it can improve pulmonary vascular remodeling and its potential efficacy in PAH as an add-on therapy to sildenafil.
To do so, the team used a rat model of PAH induced by monocrotaline. They divided the animals into 4 groups. They treated the animals in the first group with vehicle or “placebo,” those in the second group with dapagliflozin at 1 mg/kg per day, those in the third group with sildenafil at 25 mg/kg per day, and those in the fourth group with a combination of dapagliflozin and sildenafil.
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The results showed that dapagliflozin significantly reduced the increased right ventricular systolic pressure and right ventricular hypertrophy induced by monocrotaline.
Dapagliflozin also reduced the thickening of pulmonary artery media and the muscularization of pulmonary arterioles. Finally, it reduced the activation of nucleotide-binding domain-like receptor protein 3 inflammasomes in the lungs as well as the plasma levels of interleukin-1β and interleukin-18.
When the researchers analyzed the effects of dapagliflozin plus sildenafil on right ventricular systolic pressure and pulmonary vascular remodeling, they observed that the combination therapy did not have a more pronounced effect than sildenafil monotherapy.
“Further studies with different PAH models or increased treatment durations are required to confirm the beneficial effects of the combination therapy,” the researchers wrote.
Tang Y, Tan S, Li M, et al. Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension. BMC Pulm Med. 2022;22(1):142. doi:10.1186/s12890-022-01939-7