Effects of supplementation of BH4 after prolonged ischemia in skeletal muscle

Purpose: To determine whether the supplementation of tetrahydrobiopterin (BH4, 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 BH4 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 BH4 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. Conclusion: Supplementation of BH4 during reperfusion provided a significant protection against I/R injury in rat skeletal muscle. (c) 2007 Wiley-Liss, Inc.