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  • Title: Enhanced inhibition by melatonin of alpha-adrenoceptor-induced aortic contraction and inositol phosphate production in vascular smooth muscle cells from spontaneously hypertensive rats.
    Author: Wu L, Wang R, de Champlain J.
    Journal: J Hypertens; 1998 Mar; 16(3):339-47. PubMed ID: 9557927.
    Abstract:
    OBJECTIVE: To test the hypothesis that the enhanced inhibition by melatonin of the norepinephrine-induced vasoconstriction and formation of inositol phosphate in spontaneously hypertensive rats are mediated by its antioxidant effect METHODS: Aortic rings from spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were used for measuring vascular contraction forces. Cultured aortic smooth muscle cells were prelabelled with myo-[2-3H]-inositol for evaluation of formation of inositol phosphate after exposure to agonist or antagonist Basal or forskolin-induced formation of cyclic AMP was evaluated using a [3H]-cyclic AMP assay system. Oxygen-derived free radicals were generated with a hypoxanthine and xanthine oxidase system. RESULTS: The inhibition of the norepinephrine-induced aortic contraction by melatonin was more potent in spontaneously hypertensive than it was in Wistar-Kyoto rats. The inhibition of the norepinephrine-induced formation of inositol phosphate by 0.3-300 micromol/l melatonin was also greater in smooth muscle cells from spontaneously hypertensive rats than it was in those cells from Wistar-Kyoto rats. In contrast, the inhibition of the norepinephrine-induced formation of inositol phosphate in smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats by 2-iodomelatonin, an agonist of melatonin receptors, was not different. Prazosin, but not yohimbine, eliminated or partially inhibited the norepinephrine-induced formation of inositol phosphate in smooth muscle cells from Wistar-Kyoto rats or from spontaneously hypertensive rats, respectively. In the presence both of prazosin and of melatonin, the norepinephrine-induced production of inositol phosphate was abolished in smooth muscle cells from spontaneously hypertensive rats. Furthermore, superoxide dismutase significantly inhibited the norepinephrine-induced aortic contraction and formation of inositol phosphate in smooth muscle cells from spontaneously hypertensive rats, but not in those cells from Wistar-Kyoto rats. In contrast, catalase had no effect on the norepinephrine-induced formation of inositol phosphate and vascular contraction either in cells from spontaneously hypertensive rats or in cells from Wistar-Kyoto rats. Hypoxanthine-xanthine oxidase induced formation of more inositol phosphate in smooth muscle cells from spontaneously hypertensive rats than it did in those from Wistar-Kyoto rats. Melatonin and superoxide dismutase similarly inhibited the hypoxanthine-xanthine oxidase-induced formation of inositol phosphate more in cells from spontaneously hypertensive rats than it did in those from Wistar-Kyoto rats. However, melatonin had no effect either on basal or on the forskolin-induced formation of cyclic AMP in smooth muscle cells from rats of both strains. CONCLUSION: The enhanced inhibitory effect of melatonin on the norepinephrine-induced cellular production of inositol phosphate in spontaneously hypertensive rats was not mediated by melatonin receptors or alpha-adrenoceptors. Rather, the antioxidant effect of melatonin could become important in spontaneously hypertensive rats, which are suspected to have a lower cellular content of antioxidants or a greater sensitivity to superoxide anions, or both, of the vascular tissue.
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