Muscarinic‐mediated vasoconstriction in human, rat and sheep umbilical cords and related vasoconstriction mechanisms

Abstract

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 M 1 -M 5 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 largeconductance 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.Keywords Acetylcholine, BKca current, muscarinic receptor, umbilical cord vessels, vascular constriction.

New conception for the development of hypertension in preeclampsia

“…Rings of human, sheep, and rat vessels were prepared, and functional vessel experiments were performed as described [30]. Acetylcholine (10 −4 mol/L) was used for vessel relaxation experiments after application of 5-HT (10 −5 mol/L) or AII (10 −5 mol/L).…”

Roles of ion channels in regulation of acetylcholine-mediated vasoconstrictions in umbilical cords of rabbit/rats

“…Following previous reports on ACh-mediated umbilical vaso-constriction in human [28], recently, our team not only provided additional new evidence regarding ACh’s effects on human umbilical arteries and veins, but also found that ACh-induced umbilical contraction in rats and sheep [7], as the first time to demonstrate ACh-mediated umbilical vasoconstrictions in various animals. The present study extended the study and was the first to show that ACh could reliably cause contraction in umbilical vessels in rabbits too.…”

“…Based on the finding of ACh-stimulated vasoconstrictions in human, rats, sheep, and rabbits, we would like to propose that blood vessels in umbilical cords have special characters to cholinergic signals, which are very different from healthy blood vessels in other parts of the body where ACh-mediated vasorelaxation was shown. In our experiments during last 6 years, we tested at least one thousand umbilical vessels rings in various species, and observed reliable and repeatable ACh-induced vasoconstriction instead of vasorelaxation [7]. Thus, the accumulated evidence convinces us that it is reasonable to make conclusions now, that the main pharmacological effect of ACh on umbilical blood vessels is to cause vasoconstrictions, no matter in human or animals.…”

“…Acetylcholine (ACh) is the most common cholinergic chemical in the organs of the body, including the placenta and umbilical vessels [2,3] as well as in other smooth muscle cells [4–6]. Based on others’ and our studies on human umbilical arteries and veins, as well as our recent findings in rats and sheep [7], this study tested rabbit and rat umbilical cords in order to determine ACh’s special actions on umbilical vessels.…”

“…Our recent work [7] demonstrated that ACh induced reliable vasoconstrictions in human, sheep, and rats. Notably, vascular diameters can control blood and oxygen supply via umbilical vessels to fetuses [9].…”