Journal Article

VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration

Yamamoto, Naoki, Yuasa, Masato, Yagishita, Kazuyoshi, Enomoto, Mitsuhiro, Oyaizu, Takuya, Okawa, Atsushi, Horie, Masaki

2020

Overview

Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O 2 content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO 3 − , VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3–7 days and muscle healing at 5–7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/105 / 631/45/56 / 631/45/612/1221 / 692/1537/805 / 692/699/578 / 82/51 / 82/83 / 96/21 / 96/63 / Acetylcysteine - pharmacology / Angiogenesis / Angiogenesis Inducing Agents / Animals / Contusions / Contusions - genetics / Contusions - metabolism / Contusions - pathology / Contusions - therapy / Endothelial cells / Endothelial Cells - cytology / Endothelial Cells - drug effects / Endothelial Cells - metabolism / Fibroblast growth factor 2 / Fibroblast Growth Factor 2 - genetics / Fibroblast Growth Factor 2 - metabolism / Gene Expression Regulation / High pressure / Humanities and Social Sciences / Hyperbaric oxygen / Hyperbaric Oxygenation - methods / Hypoxia / Hypoxia-Inducible Factor 1, alpha Subunit - genetics / Hypoxia-Inducible Factor 1, alpha Subunit - metabolism / Hypoxia-inducible factor 1a / Macrophages / Male / multidisciplinary / Muscle, Skeletal - drug effects / Muscle, Skeletal - metabolism / Muscle, Skeletal - pathology / Muscles / Neovascularization, Physiologic - drug effects / NG-Nitroarginine methyl ester / NG-Nitroarginine Methyl Ester - pharmacology / Nitric oxide / Nitric Oxide - agonists / Nitric Oxide - biosynthesis / Nitric Oxide Synthase Type III - antagonists & inhibitors / Nitric Oxide Synthase Type III - genetics / Nitric Oxide Synthase Type III - metabolism / Nitric-oxide synthase / Oxygen / Oxygen - pharmacology / Rats / Rats, Wistar / Reactive oxygen species / Reactive Oxygen Species - agonists / Reactive Oxygen Species - antagonists & inhibitors / Reactive Oxygen Species - metabolism / Regeneration - drug effects / Science / Science (multidisciplinary) / Skeletal muscle / Treatment Outcome / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - genetics / Vascular Endothelial Growth Factor A - metabolism