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.