Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin

Abstract Background 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 (...

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Published in:Fundamental & clinical pharmacology 2024-08
Main Authors: Ayik, Seyhan, Gunata, Mehmet, Ozhan, Onural, Yildiz, Azibe, Vardi, Nigar, Sonmez, Emre, Ermis, Necip, Ates, Nilay, Kilic, Ertugrul, Noma, Samir Abbas Ali, Ulu, Ahmet, Inan, Seyfullah Taha, Acet, Haci Ahmet, Parlakpinar, Hakan
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Language:English
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Summary:Abstract Background 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.
ISSN:0767-3981
1472-8206
1472-8206
DOI:10.1111/fcp.13033