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 nitric oxide (NO) responsiveness of vascular smooth muscles in controls and SCI subjects. In eight healthy men (34 +/- 13 yr) and six SCI subjects (37 +/- 10 yr), 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. Peak diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. Resting and peak superficial femoral artery diameter in SCI subjects were smaller than in controls (P < 0.001). The FMD response in controls (4.2 +/- 0.9%) was lower than in SCI subjects (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 of SNP. However, when expressed as a relative increase within the range of diameter changes [baseline (0%) - peak diameter (100%)], both groups demonstrate similar changes in response to SNP. Changes in diameter during SNP infusion and FMD response are larger in SCI subjects compared with controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI subjects are not different from those in controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodeling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalized.