Endothelial nitric oxide synthase mediates the nitric oxide component of reflex cutaneous vasodilatation during dynamic exercise in humans

Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental V-O2,(peak) test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: (1) lactated Ringer's (control); (2) 20mmN-nitro-l-arginine methyl ester hydrochloride (non-selective NOS inhibitor); (3) 5mmN-propyl-l-arginine (nNOS inhibitor); and (4) 10mmN(5)-(1-iminoethyl)-l-ornithine dihydrochloride [endothelial NOS (eNOS) inhibitor]. Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% V-O2,(peak) for a period sufficient to raise core temperature 0.8 degrees C. At the end of cycling, all microdialysis sites were locally heated to 43 degrees C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure, skin blood flow via laser-Doppler flowmetry and core temperature via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as laser-Doppler flowmetry/mean arterial pressure and normalized to maximum. There was no significant difference between control (58 +/- 2%CVCmax) and nNOS-inhibited (56 +/- 3%CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 +/- 3%CVCmax) and non-selective NOS-inhibited (40 +/- 4%CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P<0.001 all conditions) but there was no difference between eNOS-inhibited and non-selective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with sustained dynamic exercise.