Estradiol modulates vascular response to melatonin in rat caudal artery

The purpose of this study was to determine whether estrogen modulates the f unction of vascular melatonin receptors. We used the rat caudal artery and found that the contractile effects of melatonin were influenced by the estr ous cycle, ovariectomy, and estrogen replacement. In arterial ring segments isolated from female rats, melatonin potentiated, in a concentration-depen dent manner, contractions produced either by adrenergic nerve stimulation o r by phenylephrine. Constrictor responses to melatonin were smaller in arte ries from female rats in proestrus compared with other stages of the estrou s cycle and after ovariectomy. Administration of 17 beta-estradiol to ovari ectomized female rats also resulted in decreased constriction of isolated a rteries to melatonin; however, in vitro addition of 17 beta-estradiol (10(- 7) M) had no effect. In the caudal artery, melatonin appears to act on two receptor subtypes that, mediate contraction and relaxation, respectively. T he selective melatonin MT2-receptor antagonist 4-phenyl-2-propionamidotetra line (4P-PDOT) enhanced constrictor responses to melatonin in arterial segm ents from intact female rats, consistent with the inhibition of MT2 recepto r-mediated relaxation. In contrast, 4P-PDOT had no significant effect in ar teries from ovariectomized female fats. However, when estradiol was replace d in vivo, the effect of 4P-PDOT on melatonin responses was restored. Thus circulating estradiol appears to enhance MT2 melatonin-receptor function in the thermoregulatory caudal artery of the female rat resulting in increase d vasodilatation in response to melatonin.