Agomelatine-induced responses in rat aorta

Abstract

Agomelatine is an agonist of the melatonergic MT1/MT2 receptors and an antagonist of the serotonergic 5-HT receptors. Its actions mimic melatonin in antioxidative and anti-inflammation. However, the vascular effects of agomelatine has not been investigated. In this study, we investigated the responsiveness of agomelatine on rat thoracic aorta. Cumulative addition of agomelatine (10-8-10-3 M)-induced relaxation against serotonin (5-HT, 10-6 M)-induced tone in rat aorta with and without endothelium. In different preparations the effects of nitric oxide synthase inhibitor NG nitro-L-arginine methyl esther (L-NAME, 10-4M), Ca2+-activated K+ channel blocker tetraethylammonium (TEA, 10-3M) or nonselective phosphodiesterase inhibitor 3-Isobutyl-1-methylxanthine Isobutyl-1-methylxanthine (IBMX, 10-6M) were investigated on agomelatine-induced responses. Agomelatine produced concentration-dependent relaxations of rat thoracic aorta with endothelium pre-contracted with 5-HT. Pre-incubation with L-NAME, or endothelium denudation decreased the relaxant response. In the presence of TEA, the concentration-response curve to agomelatine shifted to the right, however maximal relaxation was not significantly different from the control. Pre-treatment with IBMX increased the sensitivity to agomelatine significantly. The results indicate that nitric oxide, Ca2+-activated K+ channels and also phosphodiesterase played role in agomelatine-induced relaxation.