Pregnancy Increases Relaxation in Human Omental Arteries to the CGRP Family of Peptides.
Calcitonin gene-related peptide (CALCB) and its family members adrenomedullin (ADM) and intermedin (ADM2) play important roles in maintaining vascular adaptations during pregnancy in animal models. The present study was designed to evaluate the responses of omental arteries to CALCB, ADM, and ADM2 in pregnant and nonpregnant women, and to determine the mechanisms involved. By using resistance omental arteries collected from nonpregnant women (n = 15) during laparotomy and from term pregnant women (n = 15) at cesarean delivery, this study shows that the receptor components--calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying proteins (RAMPs) 1, 2 and 3--are localized to endothelial and smooth muscle cells in omental arteries, with increased expressions of both mRNA and protein in pregnant compared with nonpregnant women. The myography study demonstrated that CALCB, ADM, and ADM2 (0.1-100 nM) dose dependently relax U46619 (1 muM) precontracted omental artery segments, and the maximum possible effects to CALCB and ADM2, but not to ADM, are significantly enhanced in pregnant compared with nonpregnant women. Further, the vasodilatory responses to CALCB, ADM, and ADM2 are reduced by inhibitors of nitric oxide (NO) synthase (L-NAME), adenylyl cyclase (SQ22536), voltage-activated potassium channels (4-aminopyrodin and tetrabutylammonium), Ca(2+)-activated potassium channel (charybdotoxin), and cyclooxygenase (indomethacin). In conclusion, the CALCB family of peptides, CALCB and ADM2, increase human omental artery relaxation during pregnancy through diverse mechanisms, including NO, endothelium-derived hyperpolarizing factors (EDHFs) and prostaglandins, and thus could contribute to the vascular adaptations during pregnancy in the human.
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Yuanlin
Y
Dong
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Ancizar
A
Betancourt
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Madhu
M
Chauhan
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Meena
M
Balakrishnan
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Fernando
F
Lugo
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Matthew L
ML
Anderson
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Jimmy
J
Espinoza
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Karin
K
Fox
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas.
Michael
M
Belfort
Department of Obstetrics and Gynecology, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas cyallamp@bcm.edu.
Chandrasekhar
C
Yallampalli
D053607:Adrenomedullin / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D009852:Omentum / Q000098:blood supply*; D036361:Peptide Hormones / Q000494:pharmacology*; D011247:Pregnancy; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
C484330:ADM2 protein, human; D058286:Calcitonin Receptor-Like Protein; D036361:Peptide Hormones; D058261:Receptor Activity-Modifying Proteins; D053607:Adrenomedullin; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide
CALCB family peptides; human omental artery; pregnancy