Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone

• Published in: American journal of physiology. Heart and circulatory physiology 2004-01, Vol.286 (1), p.H230-H239
• Main Authors: Dong, Yuan-Lin, Vegiraju, Sujatha, Chauhan, Madhu, Gangula, Pandu R. R, Hankins, Gary D. V, Goodrum, Linda, Yallampalli, Chandra
• Format: Article
• Language: English
• Subjects: Adult; Calcitonin Gene-Related Peptide - physiology; Calcitonin Receptor-Like Protein; Female; Fetus - blood supply; Fetus - cytology; Humans; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Placenta - blood supply; Placenta - cytology; Pregnancy; Receptor Activity-Modifying Protein 1; Receptor Activity-Modifying Proteins; Receptors, Calcitonin - genetics; Receptors, Calcitonin - metabolism; RNA, Messenger - metabolism; Signal Transduction; Tissue Distribution; Vasodilation - physiology; Vasomotor System - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00140.2003

Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas 77555-1062 Submitted 19 February 2003 ; accepted in final form 22 August 2003 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 -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. pregnancy; cell signaling; vasoactivity; trophoblast; fetus Address for reprint requests and other correspondence: Y.-L. Dong, Dept. of Obstetrics and Gynecology, Univ. of Texas Medical Branch, 301 Univ. Blvd., Medical Research Bldg., Rm. 11.138, Galveston, TX 77555-1062 (E-mail: ydong{at}utmb.edu ).