Guazzelli Pedro Renato, Britto-Júnior José, Cedano Godoy P Souza Pérola Rafaella, Cardoso Vinicius Francisco, Lima Antonio Tiago, Mathias Netto Felipe Caliani, Barbosa de Souza Valéria, Antunes Edson, Schenka André, De Nucci Gilberto
Vasc Biol. 2025 Feb 19;7(1). doi: 10.1530/VB-24-0010. Print 2025 Jan 1.
To investigate the effects of the dopamine D4 receptor agonist A-412997 and the D4 antagonist sonepiprazole in human isolated umbilical artery (HUA) and vein (HUV) and the expression of the D4 receptor by immunohistochemistry in these vessels. A segment of the umbilical cord (10-20 cm) from the insertion point in the placenta and 5 cm from the umbilicus was removed by the obstetrician and placed in a container with Krebs-Henseleit solution (KHS). The Wharton's jelly was removed, and HUA and HUV rings (3 mm) were suspended in 10 mL organ baths containing oxygenated (95% O2:5% CO2) and heated (37 °C) KHS. For immunohistochemistry, the vessels were fixed in 10% formalin, embedded in paraffin wax and sectioned (4 µm). A-412997 did not induce contractions in the HUA rings. In HUA pre-contracted rings, A-412997 induced concentration-dependent relaxations, which were reduced when the HUA rings were pre-incubated with L-NAME. A-412997 caused concentration-dependent contractions of HUV rings, which were potentiated by pre-treatment with L-NAME and reduced by pre-incubation with 6-nitrodopamine. In HUV pre-contracted rings, A-412997 failed to induce relaxations. Sonepiprazole antagonized A-412997-induced contractions in HUV rings and provoked concentration-dependent relaxations in pre-contracted HUA and HUV rings. Dopamine D4 receptor was positive in both HUA and HUV, especially in the endothelium, and detected only in HUV smooth muscle cells. Activation of HUA D4 receptor is associated with relaxation, whereas in HUV, it leads to contraction. Differential expression of D4 receptors may modulate umbilical-placental blood flow.
研究多巴胺D4受体激动剂A-412997和D4拮抗剂索奈哌唑对人离体脐动脉（HUA）和脐静脉（HUV）的作用，以及通过免疫组织化学检测这些血管中D4受体的表达。产科医生从胎盘插入点取下一段脐带（10 - 20厘米），距脐部5厘米，放入含有克氏-亨氏溶液（KHS）的容器中。去除华通胶，将HUA和HUV环（3毫米）悬挂在含有含氧（95% O2:5% CO2）并加热（37°C）的KHS的10毫升器官浴中。对于免疫组织化学，将血管固定在10%福尔马林中，石蜡包埋并切片（4微米）。A-412997未引起HUA环收缩。在预收缩的HUA环中，A-412997诱导浓度依赖性舒张，当HUA环与L-精氨酸甲酯（L-NAME）预孵育时，舒张作用减弱。A-412997引起HUV环的浓度依赖性收缩，L-NAME预处理可增强收缩，6-硝基多巴胺预孵育可减弱收缩。在预收缩的HUV环中，A-412997未能诱导舒张。索奈哌唑拮抗A-412997诱导的HUV环收缩，并在预收缩的HUA和HUV环中引起浓度依赖性舒张。多巴胺D4受体在HUA和HUV中均呈阳性，尤其是在内皮中，且仅在HUV平滑肌细胞中检测到。HUA中D4受体的激活与舒张有关，而在HUV中则导致收缩。D4受体的差异表达可能调节脐-胎盘血流。
