Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone
Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone
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DOI：
10.1152/ajpheart.00140.2003
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发表时间：
2004-01-01
影响因子：
4.8
通讯作者：
Yallampalli, C
中科院分区：
文献类型：
--
作者：
Dong, YL;Vegiraju, S;Yallampalli, C
降钙素基因相关肽（CGRP）是已知最有效的内源性血管扩张剂之一，与妊娠期血管适应和胎盘功能有关。本研究旨在检测人胎盘中CGRP-A受体成分、降钙素受体样受体（CRLR）和受体活性修饰蛋白1（RAMP（1））的存在以及CGRP在胎儿胎盘循环中的血管活性。使用多克隆抗CRLR和RAMP（1）抗体对足月分娩的人胎盘进行免疫荧光染色，结果显示标记特异性集中在脐动脉/静脉、绒毛膜动脉/静脉和绒毛干血管的血管内皮和下面的平滑肌细胞以及胎盘绒毛的滋养层。体外等长收缩力测定结果显示，CGRP剂量依赖性地松弛脐动脉/静脉、绒毛膜动脉/静脉和绒毛干血管。此外，CGRP诱导的胎盘血管舒张被CGRP受体拮抗剂（CGRP（8-37））、ATP敏感性钾（K-ATP）通道阻断剂（格列本脲）和cAMP依赖性蛋白激酶A抑制剂（Rp-cAMPS）抑制，并被一氧化氮抑制剂（N-ω-硝基-L-精氨酸甲酯）部分抑制。我们认为，CGRP可能在控制人胎儿胎盘血管张力中发挥作用，CGRP引起的血管扩张可能涉及K-ATP通道、cAMP和一氧化氮通路的激活。
Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP(1)), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP(1) antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP(8-37)), ATP-sensitive potassium (K-ATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor (N-omega-nitro-L-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of K-ATP channels, cAMP, and a nitric oxide pathway.