Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;38(6):1143-1154.
doi: 10.1111/fcp.13033. Epub 2024 Aug 11.

Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin

Seyhan Ayik  1 , Mehmet Gunata  1 , Onural Ozhan  1 , Azibe Yildiz  2 , Nigar Vardi  2 , Emre Sonmez  3 , Necip Ermis  3 , Nilay Ates  4 , Ertugrul Kilic  5 , Samir Abbas Ali Noma  6 , Ahmet Ulu  6 , Seyfullah Taha Inan  1 , Haci Ahmet Acet  1 , Hakan Parlakpinar  1
Affiliations

Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin

Seyhan Ayik et al. Fundam Clin Pharmacol. 2024 Dec.

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.

Keywords: alamandine; melatonin; monocrotaline; pulmonary arterial hypertension; right ventricular systolic pressure.

PubMed Disclaimer

References

REFERENCES

    1. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67‐119. doi:10.1093/eurheartj/ehv317
    1. Dustin R, Fraidenburg AAD, Yuan JX‐J. Treatment of pulmonary arterial hypertension. In: Brunton LL, Knollmann BC, Hilal‐Dandan R, eds. Goodman & Gilman's the pharmacological basis of therapeutics. Thirteenth ed. McGraw‐Hill; 2018:573‐584. chap 31.
    1. Maarman GJ. Natural antioxidants as potential therapy, and a promising role for melatonin against pulmonary hypertension. Adv Exp Med Biol. 2017;967:161‐178. doi:10.1007/978‐3‐319‐63245‐2_10
    1. Schleifenbaum J. Alamandine and its receptor MrgD pair up to join the protective arm of the renin‐angiotensin system. Front Med. 2019;6:107. doi:10.3389/fmed.2019.00107
    1. Lautner RQ, Villela DC, Fraga‐Silva RA, et al. Discovery and characterization of alamandine: a novel component of the renin‐angiotensin system. Circ Res. 2013;112(8):1104‐1111. doi:10.1161/circresaha.113.301077

LinkOut - more resources