NO modulates norepinephrine release in human skeletal muscle: implicationsfor neural preconditioning

The purpose of this study was to estimate muscle interstitial norepinephrin e (NE) levels during exercise and to determine whether nitric oxide (NO) mo dulates NE release in the skeletal muscle in humans. We measured interstiti al dialysate concentrations of NE with two microdialysis probes inserted in to the forearm. Probes were perfused with saline and the NO synthesis inhib itor N-G-mono-methyl-L-arginine (L-NMMA), respectively. Dialysate samples w ere collected during two sequential 20-min intense dynamic handgrip periods , preceded by 40-min baseline periods. On a different day, forearm ischemia was performed instead of the first exercise period. Exercise increased dia lysate NE from 172 +/- 42 to 270 +/- 45 pg/ml (83% increase, P < 0.02, n = 6). Probes perfused with L-NMMA had a 136 <plus/minus> 39% greater dialysat e NE compared with probes perfused with saline (225 +/- 25 vs. 125 +/- 25 p g/ml, P < 0.001, n = 9). The exercise-induced increase in NE (125 <plus/min us> 52%) was attenuated if preceded by exercise (34 +/- 34%) or ischemia (4 0 +/- 36%; P = 0.06, n = 6), suggesting a neural preconditioning effect. Th is attenuation was not observed in probes perfused with L-NMMA. We propose that NO modulates NE release in skeletal muscle, that ischemic exercise inc reases muscle interstitial NE, and that this increase can be attenuated by a preconditioning effect mediated in part by NO.