Abstract
We recently demonstrated that acetylcholine (ACh) produced reliable vasoconstrictions in the umbilical cords. This study investigated the possible mechanisms with different antagonists. ACh-mediated vasoconstrictions were decreased by voltage-operated calcium (Ca(2+)) channels antagonist nifedipine or inositol-1,4,5-trisphosphate-mediated Ca(2+) release antagonist 2-aminoethyl diphenylborinate, indicating that both extracellular and intracellular calcium modulated the ACh-stimulated umbilical contraction. Intracellular Ca(2+) concentrations were increased simultaneously with vasoconstrictions by ACh in the umbilical vessels. Inhibiting large-conductance calcium-dependent potassium (BK) channels enhanced ACh-mediated contraction, whereas inhibiting voltage dependent potassium (K(+)), inward rectifier K(+) and ATP-sensitive K(+) channels had no effects. Incubation with specific K(+) channel inhibitors showed that ACh suppressed BK currents rather than 4-aminopyridine-sensitive K(+) channels currents. The results suggested that blood vessels in umbilical cords had special characteristics in response to cholinergic signals. ACh-stimulated umbilical vasoconstrictions were mediated via muscarinic receptor subtype 1/3-protein kinase C/cyclooxygenase-BK channel pathways.