title: Effects of Adrenomedullin and Glucagon-like Peptide on Distal Flap Necrosis and Vascularity: The Role of Receptor Systems and Nitric Oxide.
abstract: OBJECTIVE
  Flap necrosis in the distal area due to the deficiency of blood circulation is a major complication in flap treatment. In many previous studies, some natural substances such as chlorogenic acid, adrenomedullin (ADM), and glucagon-like peptide-1 (GLP-1) have been used to improve flap viability via their vasodilator, angiogenic, and antioxidant effects. The aim of this study is to clarify the mechanism through the use of selective antagonists for calcitonin gene-related peptide (CGRP) receptors and GLP-1 receptors such as CGRP-(8-37), exendin-(9-39), respectively, in the flap healing effects of ADM and GLP-1. The role of nitric oxide (NO) was investigated in the mechanism as well.
  
  
  METHODS
  Seventy adult female Wistar rats (200 g-250 g) were used in the study. The cutaneous skin flap (8 cm x 3 cm) on the abdominal wall was raised based on the superficial inferior epigastric artery (SIEA). Single-dose substance injections were administered into the SIEA. Necrosis in the flap area was evaluated on postoperative day 7. The proportion of the necrosis area (necrosis area % = [necrosis area/flap area] x 100) and vascularity (vascular number/cm2) in the distal area were calculated.
  
  
  RESULTS
  The administrations of ADM or GLP-1 increased the vascularity and decreased the necrosis area in the distal flap region. The ADM receptor antagonist, CGRP-(8-37), did not prevent the positive effects of ADM on flap healing and vascularity. A GLP-1 receptor antagonist, exendin-(9-39), prevented the effect of GLP-1 on flap healing and vascularity. Nitric oxide mediated the beneficial effects of both peptides on flap healing.
  
  
  CONCLUSIONS
  The CGRP receptors have no direct role, but NO acts as a mediator in the beneficial effect of ADM on flap healing. The GLP-1 specific receptors and NO act as important interagents for the effects of GLP-1 on flap healing.
authors.forename: Betul
authors.initials: B
authors.lastname: Cam
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.forename: M Ozgur
authors.initials: MO
authors.lastname: Ozyigit
authors.forename: Engin
authors.initials: E
authors.lastname: Sagdilek
authors.forename: Naciye Isbil
authors.initials: NI
authors.lastname: Buyukcoskun
authors.forename: Kasım
authors.initials: K
authors.lastname: Ozluk
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004195:Disease Models, Animal; D019074:Epigastric Arteries; D005260:Female; D000067756:Glucagon-Like Peptide Receptors / Q000378:metabolism*; D004763:Glucagon-Like Peptides / Q000494:pharmacology*; D006085:Graft Survival; D007150:Immunohistochemistry; D009336:Necrosis / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013524:Surgical Flaps / Q000098:blood supply*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000473:pathology / Q000601:surgery
chemical_list: D000975:Antioxidants; D000067756:Glucagon-Like Peptide Receptors; D018015:Receptors, Calcitonin Gene-Related Peptide; D053607:Adrenomedullin; D009569:Nitric Oxide; D004763:Glucagon-Like Peptides; D015740:Calcitonin Gene-Related Peptide