Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin.
Fundam Clin Pharmacol
; 2024 Aug 11.
Article
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| MEDLINE
| ID: mdl-39128482
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.
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Banco de datos:
MEDLINE
Idioma:
En
Revista:
Fundam Clin Pharmacol
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Turquía