Microcirculatory effects of melatonin in rat skeletal muscle after prolonged ischemia.
The purpose of this study was to determine microcirculatory effects and response of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion. Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal injection at 30 min prior to reperfusion and the same dose was given immediately after reperfusion. After reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion and endothelial-dependent and -independent vasodilatation were performed. The cremaster muscle was then harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene expression and enzyme activity. Three groups of rats were used: sham-ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with vehicle + I/R group, administration of melatonin significantly enhanced arteriole diameter, improved capillary perfusion, and attenuated endothelial dysfunction in the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm ischemia followed by reperfusion significantly depressed eNOS gene expression and constitutive NOS activity and enhanced iNOS gene expression. Administration of melatonin did not significantly alter NOS gene expression or activity in skeletal muscle after prolonged ischemia and reperfusion. Melatonin provided a significant microvascular protection from reperfusion injury in skeletal muscle. This protection is probably attributable to the free radical scavenging effect of melatonin, but not to its anti-inflammatory effect.
Department of Surgery, Division of Plastic Surgery, University of Nevada School Medicine, Las Vegas, NV 89102, USA. wzwang2000@yahoo.com
Wei Z
WZ
Wang
Xin-Hua
XH
Fang
Linda L
LL
Stephenson
Richard C
RC
Baynosa
Kayvan T
KT
Khiabani
William A
WA
Zamboni
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D004108:Dilatation, Pathologic / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D000276:Adjuvants, Immunologic; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D008550:Melatonin