Melatonin effect on the endothelial nitric oxide production in vitro and in vivo / Efeito da melatonina sobre a produção endotelial de óxido nítrico in vitro e in vivo

AUTOR(ES)

Eduardo Koji Tamura

DATA DE PUBLICAÇÃO

2009

RESUMO

Melatonin, the darkness hormone, produced at night by the pineal gland, is also synthesized in a non-rhythmic manner by other cells. Pineal and extra-pineal melatonin reaches endothelial layer, and the understanding of its mechanism of action will improve the possibilities of using this indolamine and derivates as pharmacological tools. Here we showed that melatonin, in concentrations compatible to nocturnal melatonin surge impairs the activity of eNOS, while much higher concentrations, which can be attained by activated immune competent cells, impair the induction of iNOS synthesis. As a consequence of inhibiting eNOS we showed that melatonin inhibits vasodilation of the microcirculation induced by bradykinin. The inhibitory effect of melatonin is observed only when eNOS is activated by triggering G protein-coupled receptors (bradykinin B2, muscarinic and P2Y purine receptors). Activation of eNOS by calcium-channel operated receptors (P2X) is not blocked by melatonin. Inhibition of the transcription of iNOS results in inhibition of the LPS-induced vasodilation of rat aorta. As a matter of fact, here we show that LPS effect is dependent on the endothelial layer. The mechanism of action of melatonin in inhibiting iNOS transcription is due to block of the NF-kB pathway. Our work contributed to unravel the role of endothelium cells as targets for melatonin and as a key player in the "immune-pineal axis". The understanding of the concentrations ranges reached by endogenous production, i.e., the discrimination between the levels achieved during physiological and physiopathological responses, are essential for using these substances as analogous therapeutical tools.

ASSUNTO(S)

Óxido nítrico endothelial cells nitric oxide células endoteliais melatonin melatonina

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