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.

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(?)-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. [ABSTRACT FROM AUTHOR]