Inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators

Abstract

Melatonin (MEL), the principal hormone of the vertebral pineal gland, elicits several neurobiological effects. However, the effects of MEL on vascular tissues are still vague. The first goal of this study was to investigate the effect of MEL on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline (NA) and phenylephrine (PHE) and relaxant agents (acetylcholine and sodium nitroprusside). In addition, the levels of nitric oxide (NO), cGMP, total calcium, lipid peroxides, superoxide dismutase (SOD) and glutathione (GSH) were also investigated in tissue homogenates of rabbit aortic rings preincubated (20 min) in MEL with and without contractile agents. Our results revealed that MEL has an endothelium-dependent vaso-relaxant effect and potentiated significantly the vaso-relaxant effect of acetylcholine. Moreover, MEL (10(-4) M) had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with control tissue rings, the levels of lipid peroxides were significantly increased while the levels of GSH, and SOD activities were significantly decreased in tissue homogenates of aortic rings pre-incubated (20 min) in NA or PHE. In addition, the levels of NO and cGMP were significantly lower in tissue rings pre-treated with NA and PHE, respectively. Also, the levels of total calcium were significantly increased only in tissue rings pre-treated with NA. The levels of lipid peroxides were significantly decreased, while the levels of GSH, NO and cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated (20 min) in MEL (10(-4) M) in comparison to ring tissues incubated in NA or PHE alone. In aortic rings incubated in MEL+PHE, the levels of lipid peroxides were significantly lower while the levels of GSH and cGMP and SOD activities were significantly higher than their levels in ring tissues incubated in PHE. In aortic rings incubated in MEL+NA, the levels of lipid peroxides and total calcium were significantly lower while the levels of NO were significantly higher than their levels in ring tissues incubated in NA alone. We conclude that MEL has an endothelium dependent vasorelaxant effect and potentiates the endothelium dependent vasorelaxation induced by acetylcholine. MEL inhibits the contractile responses of aortic rings to NA and PHE. These effects may be, in part, due to re-balancing the pro-oxidant/antioxidants system, lowered calcium content and elevated NO and cGMP levels in vascular tissue.