Endothelium-derived dopamine modulates EFS-induced contractions of human umbilical vessels.

José Britto‐Júnior,Alberto F O Justo,Fernanda V Mariano,David H A Pinheiro,Valéria B De Souza,Fabiola Z Mónica,André A Schenka,Guilherme M Figueiredo Murari,Edson Antunes,Gilberto De Nucci,Rafael Campos

doi:10.1002/prp2.612

Abstract

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. 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 was measured by LC‐MS‐MS. Cumulative concentration‐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 of L‐NAME, the α‐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. 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. Endothelium‐derived dopamine is a major modulator of HUCV reactivity in vitro.

Highlights

Electrical field stimulation (EFS) is a technique in which an electrical stimulus is applied uniformly to an isolated tissue in short pulse width waves.[1,2] It may cause tissue contraction or relaxation depending on the mediators released.[1,3,4] The proposed mechanism for EFS in isolated tissues is stimulation of intramural nerve endings.[5]
The endothelium of umbilical cord vessels is capable of releasing mediators capable of modulating the contractile activity induced by EFS.[9]
The results presented here clearly demonstrate, for the first time in human vessels, that human umbilical artery (HUA) and human umbilical vein (HUV) display a basal endothelium-derived dopamine release, as identified by tandem mass spectrometry

Summary

Introduction

Electrical field stimulation (EFS) is a technique in which an electrical stimulus is applied uniformly to an isolated tissue in short pulse width waves.[1,2] It may cause tissue contraction or relaxation depending on the mediators released.[1,3,4] The proposed mechanism for EFS in isolated tissues is stimulation of intramural nerve endings.[5]. Electrical field stimulation (EFS) is a technique in which an electrical stimulus is applied uniformly to an isolated tissue in short pulse width waves.[1,2]. It may cause tissue contraction or relaxation depending on the mediators released.[1,3,4]. The EFS-induced contractions of human umbilical cord vessels (HUCV) are dependent on the presence of the endothelium and are not affected by tetrodotoxin,[10] the latter indicating lack of involvement of nerve terminals. The nonselective alpha-blocker phentolamine caused a significant inhibition of EFS-induced HUCV contractions This inhibition was observed only at high concentrations, indicating that it may be acting on a different population of receptors.[10]

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