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

ABSTRACT

The aim of this study was to investigate the effect of melatonin [MEL] on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline [NA] and phenylephrine [PHE], as well as the relaxant agents [acetylcholine and sodium nitroprusside]. In addition, the levels of nitric oxide [NO], cyclic guanosine monophosphate [cGMP], total calcium, lipid peroxides, superoxide dismutase [SOD] and glutathione [GSH] were also investigated in the tissue homogenates of rabbit aortic rings pre-incubated [20 min] in MEL with and without contractile agents. The result revealed that MEL has an endothelium dependent vaso-relaxant effect and potentiated significantly the vaso-relaxant effect of acetylcholine. Moreover, MEL [10-4M] had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with the control tissue rings, the levels of lipid peroxides were significantly increased; while those of GSH and SOD activities were significantly decreased in the 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 the tissue rings pretreated with NA and PHE, respectively. The levels of total calcium were significantly increased in only tissue rings pretreated with NA. The levels of lipid peroxides were significantly decreased; while those of GSH, NO, cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated [20 min] in MEL [10-4 M] in comparison with ring tissues incubated in NA or PHE alone. In aortic rings incubated In MEL + PHE, the levels of lipid peroxides were significantly lower; while those of GSH, 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 those of NO were significantly higher than their levels in ring tissues incubated in NA alone