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

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dc.contributor.authorErmis, Necip
dc.contributor.authorOzhan, Onural
dc.contributor.authorYildiz, Azibe
dc.contributor.authorUlutas, Zeynep
dc.contributor.authorParlakpinar, Hakan
dc.contributor.authorUlu, Ahmet
dc.contributor.authorAtes, Burhan
dc.date.accessioned2026-04-04T13:33:13Z
dc.date.available2026-04-04T13:33:13Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground 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.
dc.description.sponsorshipInonu University [TDK-2017-739]
dc.description.sponsorshipThis study was funded by the Scientific Research Projects Foundation of Inonu University (Project No: TDK-2017-739). We would like to thank the Scientific Research Project unit of Inonu University for their support.
dc.identifier.doi10.1186/s12872-025-05065-0
dc.identifier.issn1471-2261
dc.identifier.issue1
dc.identifier.orcid0000-0001-9497-3468
dc.identifier.orcid0000-0001-7956-9272
dc.identifier.orcid0000-0001-6080-229X
dc.identifier.orcid0000-0001-9018-7849
dc.identifier.orcid0000-0001-6781-7478
dc.identifier.pmid40783516
dc.identifier.scopus2-s2.0-105012966586
dc.identifier.scopusqualityN/A
dc.identifier.urihttps://doi.org/10.1186/s12872-025-05065-0
dc.identifier.urihttps://hdl.handle.net/11616/108986
dc.identifier.volume25
dc.identifier.wosWOS:001549358700006
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBmc
dc.relation.ispartofBmc Cardiovascular Disorders
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectCilomilast
dc.subjectPulmonary arterial hypertension
dc.subjectTadalafil
dc.subjectMonocrotaline
dc.subjectRat
dc.titleComparison of cilomilast, tadalafil, and both drug combinations in the treatment of monocrotaline-induced pulmonary arterial hypertension in rats
dc.typeArticle

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