Characterization of vascular reactivity of human umbilical artery in normal and reduced oxygen conditions

Abstract

This study investigates the responses of the human umbilical artery to various contracting and relaxing agents in order to determine the mechanisms involved in the regulation of the umbilical cord vascular tone. Rings of human umbilical arteries from full-term caesarian deliveries were suspended in tissue baths containing warm Krebs–Henseleit buffer under normal and reduced oxygen conditions. These rings were contracted with cumulative additions of potassium chloride, serotonin, bradykinin, endothelin-1, histamine and a thromboxane A2 mimetic, U46619. Among these vasoconstrictors, only serotonin and U46619 elicited strong and sustained contractions at physiological concentrations in both oxygen conditions. Therefore, potassium chloride (50 mM), serotonin (10 µM) or U46619 (1 µM) were used to contract human umbilical arterial rings, which were then relaxed with the nitrovasodilator sodium nitroprusside, the potassium channel opener levcromakalim or the calcium antagonist amlodipine. Our data suggest that the responses of the human umbilical arteries to constricting agents, but not relaxing agents, were greater in the condition with a reduced oxygen supply. The nature of the constricting agents used did not affect the potency or efficacy of sodium nitroprusside, levcromakalim or amlodipine to relax human umbilical artery. While all three relaxing agents had similar potencies in this tissue preparation, sodium nitroprusside induced significantly smaller relaxation compared to levcromakalim and amlodi pine. These data suggest that serotonin and thromboxane A2 effectively constrict human umbilical artery at physiological concentrations. Moreover, the smooth muscle of the human umbilical artery is less responsive to vasodilators that act via the nitric oxide pathway. As such, nitric oxide donors may not be effective therapeutic agents to reduce the elevated umbilical contractile tone in pathological conditions.