Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries.
The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10(-10)-10(-5) M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10(-9)-10(-5) M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10(-7) M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A(2) analog U-46619 (10(-10)-10(-7) M). The melatonin-receptor antagonist S-20928 (10(-6) M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10(-5) M), methylene blue (10(-5) M), or N(G)-nitro-L-arginine (3 x 10(-5) M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10(-7) M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10(-9)-10(-5) M) but not by isoproterenol (10(-9)-10(-5) M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.
Yang
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Q
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, USA.
Scalbert
E
E
Delagrange
P
P
Vanhoutte
P M
PM
O'Rourke
S T
ST
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D044094:Receptors, Melatonin; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D020030:Nitric Oxide Donors; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C106874:N-(2-(1-naphthalenyl)ethyl)cyclobutanecarboxamide; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D008550:Melatonin; D007545:Isoproterenol