title: Overexpression of endothelial nitric oxide synthase in endothelial cells is protective against ischemia-reperfusion injury in mouse skeletal muscle.
abstract: Microvascular injury has been proposed to be a main cause of ischemia-reperfusion (I/R) injury. The roles of endothelial nitric oxide synthase (eNOS)-derived NO, a key regulator of vascular function, in I/R injury are incompletely understood. We used transgenic mice overexpressing eNOS in endothelial cells (eNOS-Tg) and their littermates wild-type mice (WT) to investigate the roles of eNOS in I/R injury in skeletal muscle. Superoxide levels in the affected muscles were reduced by approximately 50% in eNOS-Tg compared with WT during reperfusion. In WT, the disassembly of endothelial junctional proteins seen in the early period of reperfusion was recovered in the later phase. These findings were correlated with the increased vascular permeability in vivo. In contrast, eNOS-Tg maintained the endothelial junction assembly as well as vascular permeability during reperfusion. Leukocyte extravasation into tissue and up-regulated expression of adhesion molecules in the reperfused vessels were significantly inhibited in eNOS-Tg. Tissue viability of the affected muscle was decreased in WT time-dependently after reperfusion, whereas eNOS-Tg showed no significant reduction. NOS inhibition completely reversed these protective effects of eNOS overexpression in I/R injury. Thus, eNOS overexpression appears to prevent the I/R injury in skeletal muscle by maintaining vascular integrity.
authors.affiliation: Division of Cardiovascular and Respiratory Medicine,Department of Internal Medicine, Kobe University Graduate School ofMedicine, Kobe, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ozaki
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hirase
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Namiki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata Ki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002199:Capillary Permeability; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D002118:Calcium