Melatonin counteracts the loss of agonist-evoked contraction of aortic rings induced by incubation.
Incubation of aortic rings in a culture medium produces phenomena similar to those observed with aging, i.e. oxidative stress and inflammation leading to increased nitric oxide (NO)-mediated dilation and decreased arterial sensitivity to vasoconstrictor agents. We evaluated whether melatonin protects aortic rings from such a decrease in vasoreactivity. Two concentrations of melatonin were used: 10(-8) M, EC50 for vascular MT1-MT2 receptors, and 10(-5) M, reported as anti-oxidant. Anti-oxidant capacity, inducible nitric oxide synthase (iNOS) expression and isometric contraction of thoracic aorta rings (Wistar rats) evoked by norepinephrine (NE) were assessed. Three days of incubation of aortic rings induced iNOS expression and a fall in NE-evoked contraction. When melatonin was added to the organ bath, it (10(-5) M) increased (+96%, P < 0.05), but did not restore (compared with freshly isolated rings) NE-evoked contraction. Three days of treatment with melatonin increased (10(-8) M, +99%) or restored (10(-5) M, +216%) NE-evoked contraction (compared with freshly isolated rings). The beneficial effects of 10(-8) and 10(-5) M melatonin on NE-evoked contraction were abolished in the presence of luzindole (2 x 10(-6) M, a melatonin receptor antagonist). The incubation-induced increase in iNOS expression was reduced following 3 days of melatonin administration (10(-8) and 10(-5) M). Melatonin (10(-5) M) increased catalase activity (6550 +/- 256, P < 0.05 vs. nontreated fresh aortic rings 5554 +/- 444 nmol min(-1) mg protein(-1)). In conclusion, melatonin counteracts the incubation-induced loss of agonist-evoked contraction of aortic rings by a specific receptor-mediated phenomenon involving iNOS expression; at higher melatonin concentrations, an anti-oxidant effect is probably also involved.
Lartaud
Isabelle
I
Pharmacology Laboratory, Faculté de Pharmacie, Université Henri Poincaré Nancy-1, 5 rue Albert Lebrun, 54001 Nancy Cedex, France.
Faure
Sébastien
S
Tabellion
Aurore
A
Resende
Angela C
AC
Nadaud
Sophie
S
Bagrel
Denyse
D
Capdeville-Atkinson
Christine
C
Atkinson
Jeffrey
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D003470:Culture Media; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin; D009638:Norepinephrine