Role of Melatonin in Attenuation of Vascular Angiotensin 1-7 Reactivity Via Calcium Channels and Endothelial Derived Relaxing Factors in Induced Diabetic Aortic Rats

Abstract

Melatonin (MEL) appears to have a regulatory role in vascular tone through enhancing endothelial-derived relaxing factors (EDRFs) and modulation of calcium (Ca²⁺) influx in both vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs). While, such effects on angiotensin 1-7 (Ang 1-7) vasoreactivity in the vascular endothelial dysfunction (VED) remained unclear. Therefore, the current study investigates the vasculoprotective action of MEL on Ang 1-7 dose response curve (DRC) via Ca²⁺ channels and EDRFs in streptozotocin (STZ)–induced diabetes mellitus (DM) in male albino rats’ isolated aorta. The present study included four experiments. Experiment I, included measurement of tunical intima-media thickness and the histological examination in non-DM, STZ-induced DM and STZ-induced DM treated with MEL. Experiment II included the measurement of the isometric tension using Ang 1-7 DRC with or without N^G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) inhibitor in the studied groups. Experiment III included the measurement of the isometric tension using Ang 1-7 DRC with or without indomethacin (IND), a non-selective cyclooxygenase (COX) inhibitor in the studied groups. Experiment IV included the measurement of the isometric tension using Ang 1-7 DRC with or without nifedipine (NIF), a voltage-dependent L-type Ca²⁺ channels blocker in the studied groups. The present study found that, MEL demonstrated protective effects against vascular stress through multiple mechanisms. These actions collectively contributed to the maintenance of vascular health, preservation of endothelial function, and prevention of vascular diseases. Also it modulated vascular response to Ang 1-7 by either antioxidant properties or Ca²⁺ vasomotion.