Melatonin and vitamin C increase umbilical blood flow via nitric oxide-dependent mechanisms
Article first published online: 24 SEP 2010
© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S
Journal of Pineal Research
Volume 49, Issue 4, pages 399–406, November 2010
How to Cite
Thakor, A. S., Herrera, E. A., Serón-Ferré, M. and Giussani, D. A. (2010), Melatonin and vitamin C increase umbilical blood flow via nitric oxide-dependent mechanisms. Journal of Pineal Research, 49: 399–406. doi: 10.1111/j.1600-079X.2010.00813.x
- Issue published online: 18 OCT 2010
- Article first published online: 24 SEP 2010
- Received June 11, 2010; accepted August 20, 2010.
- umbilical blood flow;
- vitamin C
Abstract: Inadequate umbilical blood flow leads to intrauterine growth restriction, a major killer in perinatal medicine today. Nitric oxide (NO) is important in the maintenance of umbilical blood flow, and antioxidants increase NO bioavailability. What remains unknown is whether antioxidants can increase umbilical blood flow. Melatonin participates in circadian, seasonal, and reproductive physiology, but has also been reported to act as a potent endogenous antioxidant. We tested the hypothesis that treatment during pregnancy with melatonin increases umbilical blood flow via NO-dependent mechanisms. This was tested in pregnant sheep by investigating in vivo the effects on continuous measurement of umbilical blood flow of melatonin before and after NO blockade with a NO clamp. These effects of melatonin were compared with those of the traditional antioxidant, vitamin C. Under anesthesia, 12 pregnant sheep and their fetuses (0.8 of gestation) were fitted with catheters and a Transonic probe around an umbilical artery, inside the fetal abdomen. Following 5 days of recovery, cardiovascular variables were recorded during fetal i.v. treatment with either melatonin (n = 6, 0.5 ± 0.1 μg/kg/min) or vitamin C (n = 6, 8.9 ± 0.4 mg/kg/min) before and after fetal NO blockade with the NO clamp. Fetal treatment with melatonin or vitamin C increased umbilical blood flow, independent of changes in fetal arterial blood pressure. Fetal NO blockade prevented the increase in umbilical blood flow induced by melatonin or vitamin C. Antioxidant treatment could be a useful clinical tool to increase or maintain umbilical blood flow in complicated pregnancy.