Protective effects of melatonin on AT1, ACE2, and Mas genes expression in induced diabetic aortic rats

Abstract

Diabetes mellitus (DM) is considered a threat to the vascular tone. Melatonin (MEL) exhibits broad-spectrum effects across multiple organs and displays pleiotropic characteristics. The present study aims to investigate the vascular influence of MEL administration either in vivo or in vitro on isolated thoracic aortic Mas receptor (MasR), angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme 2 (ACE2) gene expressions of induced diabetic rats by streptozotocin (STZ). The thoracic aortae were isolated in order to investigate the influence of MEL on MasR, AT1R, and ACE2 gene expression by real-time PCR (BIO-RAD), and dose-response curve (DRC) was also measured for MEL, angiotensin 1-7 (Ang 1-7) reactivity with or without MasR blocker (A779), angiotensin 1-8 (Ang 1-8) reactivity with or without AT1R blocker, valsartan (VAL) and ACE2 inhibitor by ADInstrument organ bath (Panlab apparatus, Harvard University, USA), also the present study includes the pathohistological examination of thoracic aortae tissue. Three groups of male albino rats were divided randomly into non-diabetic rats (non-DM), STZ-induced diabetes (DM), and STZ-induced diabetes treated with MEL. The DM rat's aortae exhibited a slight decrease of AT1R gene expression and a slight increase of both Maser and ACE2 gene expression, while in STZ-induced DM treated with MEL these targeted genes were slightly restored. Melatonin has shown positive effects on the gene expression of ACE2, AT1R, and MasR and has influenced the reactivity of Ang 1-7 and Ang 1-8 in the aortas of diabetic rats through distinct mechanisms.

Keywords

• at1r
• ace2
• ang 1-8
• melatonin
• masr