Melatonin attenuates responses to angiotensin II in isolated aortic rings of STZ-induced type 1-like DM rats.

Abstract

Background: In patients with diabetes mellitus (DM), vascular endothelial dysfunction (VED) is the main reason for impaired life expectancy. Melatonin (MEL) demonstrates wide-ranging effects across various organs and exhibits pleiotropic characteristics. The current study aims to investigate the modulatory roles of MEL vascular response to angiotensin II (Ang II) and its receptors including angiotensin type 1 receptor (AT-1 R) and angiotensin type 2 receptor (AT-2 R) in isolated thoracic aorta of non-diabetes (non-DM) and diabetes (DM) rats.

Methods: The thoracic aortae were isolated in order to investigate the influence of MEL on AT-1 R, using valsartan (VAL) and MT-2Rusing luzindole (LUZ) via dose-response curve (DRC) measurement of Ang II reactivity. In addition, AT-1 R was involved in this study, under PD123319 with ADInstrument organ bath (Panlab apparatus, Harvard University, USA).

Results: The maximum response of Ang II was increased significantly in DM condition. In addition, AT-1 R was completely blocked under VAL, while AT-2 R was upregulated in the DM group. The combination of VAL and PD123319 led to abolishing the Ang II effect dramatically as well. Melatonin alone reduced Ang II in the DM group dramatically. This effect was also observed with MEL, PD1213319, and VAL combination, as well as, with MEL, LUZ, and PD1213319 combination.

Conclusions: Melatonin has been demonstrated to modulate both AT-1 R and AT-2 R and has influenced the reactivity of Ang II in the aortas of diabetic rats through highly complex mechanisms.