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We tested the hypothesis that selective nNOS inhibition via S-methyl-l-thiocitrulline (SMTC) would reduce rat hindlimb skeletal muscle blood flow and vascular conductance (VC) during high-speed treadmill running above critical speed (asymptote of the http://www.selleckchem.com/products/epacadostat-incb024360.html hyperbolic speed versus time-to-exhaustion relationship for high-speed running and an important glycolytic fast-twitch fibre recruitment boundary in the rat) principally within glycolytic fast-twitch muscle. Six rats performed three high-speed treadmill runs to exhaustion to determine critical speed. Subsequently, hindlimb skeletal muscle blood flow (radiolabelled microspheres) and VC (blood flow/mean arterial pressure) were determined during supra-critical speed treadmill running (critical speed + 15%, 52.5 �� 1.3 m min?1) before (control) and after selective nNOS inhibition with 0.56 mg kg?1 SMTC. SMTC reduced total hindlimb skeletal muscle blood flow (control: 241 �� 23, SMTC: 204 �� 13 ml min?1 (100 g)?1, P http://www.selleckchem.com/products/i-bet-762.html These results extend our understanding of vascular control during exercise by identifying fibre-type-selective peripheral vascular effects of nNOS-derived NO during high-speed treadmill running. Abbreviations? eNOS endothelial nitric oxide synthase HR heart rate l-NAME NG-nitro-l-arginine-methyl-ester MAP mean arterial pressure nNOS neuronal nitric oxide synthase NO nitric oxide NOS nitric oxide synthase SMTC S-methyl-l-thiocitrulline VC vascular conductance The ability of the cardiovascular http://www.selleck.cn/products/lee011.html system to increase skeletal muscle blood flow and, therefore, O2 delivery during exercise is accomplished via neurohumoral activation (to increase cardiac output and initiate blood flow redistribution) and local mechanical and vasomotor control mechanisms (reviewed by Joyner & Wilkins, 2007). The robust active muscle blood flow response supports sustained exercise performance whereas many disease processes are hallmarked by O2 delivery impairment and exercise intolerance (e.g. heart failure, reviewed by Poole et al. 2012). NO is an important cardiovascular signalling molecule that has been reported to play an integral role in promoting exercise hyperaemia in animals (Hirai et al. 1994; King et al. 1994) and humans (Schrage et al. 2004). In healthy subjects NO is synthesized enzymatically via nNOS (type I) or endothelial nitric oxide synthase (eNOS; type III). The vasodilatory contributions of eNOS-derived NO secondary, at least in part, to vascular endothelial shear stress during exercise are well known (reviewed by Green et al. 1996).