The mode of vasorelaxing action of melatonin in rabbit aorta.
1. The vasorelaxing effect of melatonin on the contractile response to 5-hydroxytryptamine (5-HT) was investigated in rabbit isolated aorta. 2. Melatonin (10(-5)-10(-3) M) caused relaxation of the 5-HT (10 M) response in a concentration-dependent manner. Nifedipine (10(-6) M) did not affect the relaxing action of melatonin. 3. Pretreatment with methylene blue (10(-5) M) or nitroglycerin (3 x 10(-8) M) inhibited or potentiated, respectively, the relaxing action of melatonin. 4. Pretreatment with melatonin (10(-3) M) or M&B 22.948 (10(-3) M) potentiated the relaxing effect of nitroglycerin (10(-9)-10(-5) M) on the contraction induced by PGF2 alpha (4 x 10(-6) M). The effect of a combined treatment with melatonin and M&B 22.948 was not significantly different from that of a single treatment with M&B 22.948. 5. Melatonin (10(-5)-10(-3) M) inhibited the activity of cGMP-phosphodiesterase, in a concentration-dependent manner. 6. These results suggest that the vasorelaxing action of melatonin may be due to an increase in the level of cGMP.
Satake
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Department of Pharmacology, University of Hawaii, John A. Burns School of Medicine, Honolulu 96822.
Oe
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Sawada
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Shibata
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D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D005996:Nitroglycerin / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
D011688:Purinones; D012701:Serotonin; D015237:Dinoprost; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D005996:Nitroglycerin; C011145:zaprinast; D008550:Melatonin; D008751:Methylene Blue