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.