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Review
. 2025 Jun;62(6):801-809.
doi: 10.1007/s00592-025-02479-2. Epub 2025 Mar 13.

The interactions between melatonin and the renin-angiotensin system (RAS) in vascular attenuation in diabetic and non-diabetic conditions

Nazar M Shareef Mahmood  1 , Almas M R Mahmud  2 , Ismail M Maulood  2
Affiliations
Review

The interactions between melatonin and the renin-angiotensin system (RAS) in vascular attenuation in diabetic and non-diabetic conditions

Nazar M Shareef Mahmood et al. Acta Diabetol. 2025 Jun.

Abstract

Background: The hormone melatonin (MEL), primarily acknowledged for its role in regulating circadian rhythms, has demonstrated itself to be a complicated molecule with significant implications for vascular physiology. Melatonin exerts extensive physiological effects directly via the MEL receptor type 1 (MT1R) and the MEL receptor type 2 (MT2R), as well as indirectly through the improvement of antioxidant vascular tone.

Objective: This review aims to analyse the intricate relationships between MEL and the renin-angiotensin system (RAS) in the vascular attenuation of non-diabetic (non-DM) and diabetic (DM) contexts. Alterations in the expression of RAS components and their dysregulation are prevalent in diabetes. Melatonin exhibits vasoprotective advantages in non-diabetic conditions. In the context of DM, vascular problrms such as vascular endothelial dysfunction (VED), hypertension, and atherosclerosis result from the dysregulation of MEL-RAS interactions. Comprehending the actions of MEL on RAS components in diabetes vasculature is essential for formulating tailored pharmaceutical therapy methods.

Conclusion: This review consolidates existing knowledge regarding the vascular effects of MEL in relation to RAS activation, emphasising its potential role as a modulating factor for angiotensin 1-8 (Ang 1-8), angiotensin-converting enzyme 2 (ACE2), and angiotensin 1-7 (Ang 1-7) in the management of vascular complications associated with DM.

Keywords: Diabetes mellitus; MT1R; MT2R; Melatonin; RAS.

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Conflict of interest statement

Declarations. Conflict of interest: All the authors declare that there are no conflicts of interest regarding the publication of this manuscript.

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