Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined NO-responsiveness of vascular smooth muscles in controls and SCI subjects. METHODS: In 8 healthy men (34±13 years) and 6 SCI subjects (37±10 years), superficial femoral artery FMD-response was assessed by echo-Doppler. Subsequently, infusion of incremental dosages of sodium-nitroprusside (SNP) was used to assess NO-responsiveness. Maximal diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. RESULTS: Resting and maximal superficial femoral artery diameter in SCI were smaller than in controls (P<0.001). The FMD-response in controls (4.2±0.9%) was lower than in SCI (8.2±0.9%, P<0.001), but not after correcting for area-under-the-curve for shear rate (P=0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose SNP. However, when expressed as a relative increase within the range of diameter changes (baseline[0%]-maximal diameter[100%]), both groups demonstrate similar changes in response to SNP. CONCLUSION: Changes in diameter during SNP infusion and FMD-response are larger in SCI compared to controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI are not different from controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodelling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalised.