Endothelium-derived dopamine modulates EFS-induced contractions of human
umbilical vessels
Abstract
Background and purpose: Electrical field stimulation (EFS) induces
contractions of both snake aorta and human umbilical cord vessels (HUCV)
which were dependent on the presence of the endothelium. This study
aimed to establish the nature of the mediator(s) responsible for
EFS-induced contractions in HUCV. Experimental approach: Rings with or
without endothelium from human umbilical artery (HUA) or vein (HUV) were
mounted in organ bath chambers containing oxygenated, heated
Krebs-Henseleit’s solution. Basal release of dopamine (DA),
noradrenaline and adrenaline were measured by LC-MS-MS. Cumulative
dose-response curves were performed with dopamine in the absence and in
the presence of L-NAME or of dopamine antagonists. EFS studies were
performed in the presence and absence L-NAME, the alpha-adrenergic
blockers prazosin and idazoxan and the dopamine antagonists SCH-23390
and haloperidol. Tyrosine hydroxylase (TH) and dopa-decarboxylase (DDC)
were studied by immunohistochemistry and fluorescence in-situ
hybridizations. Key Results: Basal release of dopamine requires an
intact endothelium in both HUA and HUV. TH and DDC are present only in
the endothelium of both HUA and HUV as determined by
immunohistochemistry. Dopamine induced contractions in HUA only in the
presence of L-NAME. Dopamine-induced contractions in HUV were strongly
potentiated by L-NAME. The EFS-induced contractions in both HUA and HUV
were potentiated by L-NAME and inhibited by the D2-like receptor
antagonist haloperidol. The α-adrenergic antagonists prazosin and
idazoxan and the D1-like receptor antagonist SCH-23390 had no effect on
the EFS-induced contractions of HUA and HUV. Conclusion and
Implications: Endothelium-derived dopamine is a major modulator of HUCV
reactivity in vitro.