Ayık, SeyhanGünata, MehmetÖzhan, OnuralYıldız, AzibeAteş, NilayKılıç, ErtuğrulParlakpınar, Hakan2025-11-102025-11-102024Ayık, S., Günata, M., Özhan, O., Yıldız, A., Ateş, N., Kılıç, E. ... Parlakpınar, H. (2024). Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin. Fundamental and Clinical Pharmacology, 38(6), 1143-1154. http://dx.doi.org/10.1111/fcp.130330767-39811472-8206http://dx.doi.org/10.1111/fcp.13033https://hdl.handle.net/20.500.12511/13182Background: Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor. Objectives: We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH. Methods: The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed. Results: Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it. Conclusion: ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.eninfo:eu-repo/semantics/openAccessAlamandineMelatoninMonocrotalinePulmonary Arterial HypertensionRight Ventricular Systolic PressureArticle3861143115410.1111/fcp.13033Q3WOS:0012882096000012-s2.0-8520102242139128482Q2