Effects of supplementation of BH4 after prolonged ischemia in skeletal muscle.
OBJECTIVE
To determine whether the supplementation of tetrahydrobiopterin (BH(4), an essential cofactor of nitric oxide synthase; NOS) could attenuate endothelial dysfunction and improve NOS activity and cell viability in skeletal muscle after ischemia/reperfusion (I/R).


METHODS
A vascular pedicle isolated rat cremaster muscle model was used. Cremaster muscles were subjected to 4 h of ischemia followed by 2 h of reperfusion. Rats were given either normal saline or BH(4) by intravenous injection at 1 min prior to reperfusion. After reperfusion, average arteriole diameter, capillary perfusion, endothelial-dependent/-independent vasodilatation, NOS activity, and muscle cell viability were evaluated.


RESULTS
Supplementation of BH(4) prior to reperfusion significantly attenuated reperfusion-induced vasoconstriction, poor capillary perfusion, and endothelial dysfunction and enhanced cNOS activity and slightly improved cell viability in the skeletal muscle after I/R.


CONCLUSIONS
Supplementation of BH(4) during reperfusion provided a significant protection against I/R injury in rat skeletal muscle.
Wang
Wei Z
WZ
Division of Plastic Surgery, Department of Surgery, University of Nevada School of Medicine, Las Vegas, NV 89102, USA. wzwang2000@yahoo.com
Fang
Xin-Hua
XH
Stephenson
Linda L
LL
Khiabani
Kayvan T
KT
Zamboni
William A
WA
D000818:Animals; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D001708:Biopterins; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin