Role of Melatonin in Attenuation of Vascular Ang 1–7 Reactivity via Oxidative Stress Enzymes and PI3K/AKT/eNOS Signalling Pathways in Induced Diabetic Rats
Volume 81, Issue 2 (2023): Veterinarija ir Zootechnika, pp. 8–21
Pub. online: 21 August 2024
Type: Research Article
Open Access
Open Access
Received
26 September 2023
26 September 2023
Revised
11 December 2023
11 December 2023
Accepted
18 December 2023
18 December 2023
Published
21 August 2024
21 August 2024
Abstract
Diabetes mellitus (DM) is considered as the main complication of the cardiovascular
system leading to vascular endothelial dysfunction (VED). Besides, melatonin (MEL) has been
known to improve the vascular tone directly or indirectly with MEL receptors (MT1R and MT2R) and
antioxidant properties, respectively. The rings were extracted from three groups including non-diabetes
(non-DM), streptozotocin induced diabetes (STZ-induced DM) and STZ-induced DM treated with
MEL (DM+MEL) in male albino rats. The experimental procedure includes thoracic aortic vascular
reactivity of angiotensin 1–7 (Ang 1–7) and histological examination. The vascular reactivity was
conducted across eight distinct groups, encompassing RO-31-8220 (5 μM), protein kinase C (PKC)
inhibitor, Apocyanin [(APO, 10 micromolar (μM)], the nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase inhibitor, rotenone (ROT 50 μM), mitochondrial complex I electron transport chain
inhibitor, oxypurinol (OXY, 100 μM), xanthine oxidase inhibitor, PI-3065 (1 μM), phosphoinositide
3-kinases (PI3K) inhibitor, Ipatasertib (1 μM), protein kinase B (AKT) inhibitor, A779 (1 μM), the
Mas receptor blocker and N(ω)-nitro-L-arginine methyl ester (L-NAME 200 μM), the nitric oxide
(NO) inhibitor pre-incubation. However, it is worth noting that the pre-incubation with OXY resulted
in a notably significant rightward shift in this response. Conversely, in the STZ-induced DM group,
there was a notable significant rightward shift observed in response to each of APO, ROT, and OXY.
MEL appeared to regulate the vascular tone within Ang 1–7 modulation in STZ-induced DM rats.
Therefore, MEL could offer many vascular benefits within Ang 1–7 under diabetic condition.