Is acetylcholine constriction of umbilical vessels clinically relevant?

Abstract

Umbilical cord vessels lack innervation, yet they constrict immediately following delivery. This is obviously an important response and is observed across many mammalian species. The precise mechanism of the vasoconstriction is unknown, but temperature changes, changes in oxygen tension and mechanical traction on the cord are generally accepted stimuli which elicit this vasoconstriction response. It is also widely believed that the regulation of vascular smooth muscle tension is mediated via vasoactive substances within the circulation or through local production of these substances within the vessel wall. Acetylcholine, a vasodilator, has been shown to induce endothelium-dependent vascular smooth muscle relaxation in different species and in different vascular beds (Furchgott and Zawadski, Nature 1980;288:373–6). In contrast, other investigators have shown that acetylcholine induces vasoconstriction of human umbilical cord arteries and veins (Altura et al. Am J Physiol 1972;222:345–55). Although other autacoids induced more potent constriction than acetylcholine in most vascular beds, the finding that acetylcholine exerted a vasoconstrictive effect on umbilical cord vessels raises the question of whether such a vasoactive effect may have clinical implications. In a series of elegant experiments, the present authors investigated the potential mechanisms through which this effect may be mediated. They confirmed the contrasting vasodilatory and constrictive properties of acetylcholine in human, sheep and rat umbilical cord preparations, and, more importantly, they unravelled some of the physiological mechanisms involved, including a role for potassium and calcium currents, and muscarinic receptor subtypes. Their findings are preliminary and yet to be corroborated by others; however, they raise the question of whether acetylcholine-induced vasoconstriction of umbilical cord vessels may be conserved across mammalian species. Although the investigators also examined umbilical cord vessels from pregnancies complicated by diabetes and hypertension, they provided no data nor speculated on any differences in cord vessel responses between these complicated pregnancies and their normal counterparts. Their elaboration of the mechanisms involved in acetylcholine-induced vasoconstriction also highlights another layer of complexity. For example, acetylcholine induced further vasoconstriction in preparations which were pre-constricted with potassium chloride, serotonin or prostaglandin E2. In spite of this, the situation is likely to be different in vivo. The umbilical cord vessels are believed to be almost maximally dilated in vivo and it is unknown to what extent acetylcholine maintains smooth muscle tone in the umbilical cord vessels. Therefore, these results should be interpreted with caution. A major part of the vascular resistance in the feto-placental circulation is presumed to be located in the resistance vessels of the placental villi. Acetylcholine induced a relaxant response in vascular preparations from human stem villi arteries in vitro (Sabry et al. Fundam Clin Pharmacol 1995;9:46–51), but did not induce changes in the perfusion pressure of isolated and perfused human placental cotyledons (Amarnani et al. Am J Physiol 1999;277:H842–7). Furthermore, in vitro preparations of human umbilical cord vessels used in experiments on autacoid responsiveness are unavoidably sampled after birth when the preparations are already constricted. These preparations are therefore not necessarily representative of the in vivo situation. In summary, the current study provides valuable data on the physiology and regulation of umbilico-placental blood flow; however, the jury is still out on the clinical importance of acetylcholine in human umbilical cord circulation. The author has no conflicts of interest.