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Muscarinic-mediated vasoconstriction in human, rat and sheep umbilical cords and related vasoconstriction mechanisms
1Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, China.
Objective:
The umbilical cord provides nutrition and oxygen to the fetus. The aim of this study was to determine the effects of acetylcholine (ACh) on umbilical cords from humans and other mammals, and the mechanisms of ACh-mediated vasoconstriction in the human umbilical cord.
Design:
Human and animal umbilical cords used in vascular and cellular experiments.
Setting:
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Population:
A total of 85 pregnant women, 16 Sprague Dawley rats and seven pregnant sheep.
Methods:
Umbilical cord veins and arteries from humans, rats and sheep, aortas and mesenteric arteries from rats, and mesenteric, carotid and femoral arteries from ovine fetuses were used to compare vascular functions in response to ACh and to determine the mechanisms of ACh-mediated umbilical vasoconstriction. Vascular tension and ion channel currents were measured on isolated vessels and smooth muscle cells from human umbilical cords.
Main Outcome Measures:
Provision of new evidence to conclude that ACh-stimulated vasoconstriction is common to all umbilical cords, and cellular mechanisms are linked to potassium channels.
Results:
ACh caused reliable vasoconstriction in umbilical veins/arteries in humans, rats and sheep, but not in any other vessels, including fetal vessels. Atropine inhibited the effects of ACh. The mRNA of ACh-muscarinic receptor subtypes M1 -M5 was expressed in human umbilical vessels. The protein kinase C antagonist GF109203X and the calcium inhibitor nifedipine decreased ACh-induced vasoconstriction in human umbilical vessels. ACh also caused a reduction in whole-cell potassium channel currents and the single-channel current of large-conductance calcium-activated potassium (BKca) channels.
Conclusion:
Umbilical vessels are significantly different from other vessels in their response to ACh. BKca channels in smooth muscle cells may play important roles in ACh-mediated vasoconstriction in human umbilical cords. This information may be important for fetal medicine and practice with regard to the effect on fetal development of umbilical vascular functions.
