Comparison of cilomilast, tadalafil, and both drug combinations in the treatment of monocrotaline-induced pulmonary arterial hypertension in rats.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and inflammation. This study aimed to evaluate the effects of cilomilast (CIL), a phosphodiesterase-4 inhibitor, and tadalafil (TAD), a phosphodiesterase-5 inhibitor, on PAH induced by monocrotaline (MCT) in rats. METHODS: Forty Wistar albino rats were divided into five groups: control, MCT, MCT + CIL, MCT + TAD, and MCT + CIL + TAD. PAH was induced via MCT, and treatments were administered orally from days 21 to 35. Hemodynamic parameters, right ventricular pressure (RVP), echocardiographic findings, and histopathological lung and heart tissue changes were assessed. Nitric oxide (NO) levels in lung tissue were also measured. RESULTS: Tissue NO levels were significantly greater in the MCT + CIL + TAD group than in the MCT group (p = 0.01). The RVP was lower in the MCT + TAD and MCT + CIL + TAD groups than in the MCT group (p < 0.05) but not in the MCT + CIL group. Histopathologically, lung perivascular infiltration and pulmonary artery wall thickness were significantly reduced in the MCT + CIL + TAD group, indicating an anti-inflammatory effect. However, CIL alone did not significantly impact pulmonary artery thickening or RVP. CONCLUSION: CIL alone had no significant effect on PAH progression, but its combination with TAD improved inflammation scores and NO levels. These findings suggest that targeting inflammation alongside vasodilation may offer therapeutic benefits in PAH. Further studies with different doses and PAH models are recommended.