The influence of several classes of drugs on the melatonin-induced vasorelaxation of isolated rat aorta were examined. Melatonin caused a dose-dependent relaxation of precontracted (30 mM KCl) aorta. This relaxant response was blocked by preincubating vessels with antagonists of vasoactive intestinal peptide. Substance P antagonists did not alter the response to melatonin. Pretreatment of vessels with 6-hydroxydopamine, lidocaine, or tetrodotoxin antagonized the relaxant response to melatonin. On the other hand, pretreatment with atropine + propranolol did not alter the response to melatonin. These experiments suggest that melatonin may exert part of its vasoactive actions by an interaction with perivascular nerve terminals.
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