1. Effects of adrenomedullin and glucagon-like peptide on distal flap necrosis and vascularity: The role of receptor systems and nitric oxide
- Author
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Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi., Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Biyofizik Anabilim Dalı., Cam, Betül, Bağdaş, Deniz, Özyiğit, Musa Özgür, Sağdilek, Engin, Büyükcoşkun, Naciye İsbil, Özlük, Kasım, AAH-1692-2021, AAH-2873-2021, AAR-6478-2021, and AAH-4397-2021
- Subjects
Rats, wistar ,Glucagon-like peptides ,Survival ,Physiology ,Glucagon like peptide receptor ,Apoptosis ,Injury ,Wistar rat ,Disease models, animal ,Antioxidants ,Adrenomedullin ,Endothelial growth-factor ,Pathology ,Calcitonin gene related peptide receptor ,Cell-proliferation ,Graft survival ,Flap necrosis ,Immunohistochemistry ,Glucagon like peptide ,Receptors, calcitonin gene-related peptide ,Flaps (Control Surfaces) ,Perforator Flap ,Reperfusion Injury ,Calcitonin gene-related peptide ,A signaling pathway ,Rat model ,Female ,Antioxidant ,Skin flaps ,Glucagon-like peptide-1 ,Beta-cells ,Wound healing ,Dermatology ,Necrosis ,Animals ,Glucagon-like peptide receptors ,Animal ,Disease model ,Wounds and injuries ,Vascularization ,Epigastric arteries ,Nitric oxide ,Protein-kinase ,Rats ,Drug effect ,Epigastric artery ,Metabolism ,Surgical flaps ,Rat ,Surgery ,Angiogenesis ,Calcitonin gene related peptide - 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. Materials and 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/cm(2)) 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. Conclusion. 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.
- Published
- 2017