Calcitonin Gene Related Peptide, Adrenomedullin, and Adrenomedullin 2 Function in Uterine Artery During Human Pregnancy

• Published in: Endocrinology (Philadelphia) 2022-01, Vol.163 (1), p.1
• Main Authors: Chauhan, Madhu, Betancourt, Ancizar, Balakrishnan, Meena, Mishra, Akansha, Espinosa, Jimmy, Shamshirsaz, Alireza A, Fox, Karin, Belfort, Michael, Yallampalli, Chandra
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adenylate cyclase; Adrenomedullin; Adrenomedullin - physiology; Apamin; Calcitonin; Calcitonin gene-related peptide; Charybdotoxin; Dimerization; Dose-Response Relationship, Drug; Endocrinology; Endothelium; Female; Gene expression; Genes; Humans; In Vitro Techniques; Kinases; Mediation; Membrane Proteins - metabolism; mRNA; Myocytes, Smooth Muscle - metabolism; NG-Nitroarginine methyl ester; Nitric oxide; Peptide Hormones - physiology; Peptides; Pregnancy; Pregnant women; Protein-tyrosine kinase; Receptor activity modifying proteins; Receptor Activity-Modifying Protein 1 - metabolism; Receptor Activity-Modifying Protein 2 - metabolism; Receptor Activity-Modifying Protein 3 - metabolism; Receptors; Receptors, Calcitonin - metabolism; RNA; RNA, Messenger - metabolism; Segments; Smooth muscle; Tumor necrosis factor-α; Tyrosine; Uterine Artery - metabolism; Uterus; Vascular Endothelial Growth Factor Receptor-1 - metabolism
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endocr/bqab204

Rationale Calcitonin gene-related peptide (CGRP) and its family members adrenomedullin (ADM) and adrenomedullin 2 (ADM2; also known as intermedin) support vascular adaptions in rat pregnancy. Objective This study aimed to assess the relaxation response of uterine artery (UA) for CGRP, ADM, and ADM2 in nonpregnant and pregnant women and identify the involved mechanisms. Findings (1) Segments of UA from nonpregnant women that were precontracted with U46619 (1μM) in vitro are insensitive to the hypotensive effects of CGRP, ADM, and ADM2; (2) CGRP, ADM, and ADM2 (0.1-100nM) dose dependently relax UA segments from pregnant women with efficacy for CGRP > ADM = ADM2; (3) the relaxation responses to CGRP, ADM, and ADM2 are differentially affected by the inhibitors of nitric oxide (NO) synthase (L-NAME), adenylyl cyclase (SQ22536), apamin, and charybdotoxin; (4) UA smooth muscle cells (UASMC) express mRNA for calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)1 and RAMP2 but not RAMP3; (5) receptor heterodimer comprising CRLR/RAMP1 and CRLR/RAMP2 but not CRLR/RAMP3 is present in UA; (6) soluble fms-like tyrosine kinase (sFLT-1) and TNF-α treatment decrease the expression of RAMP1 mRNA (P