The purpose of this investigation was to assess the interactive influence of sympathetic activation and supplemental NO on brachial artery distensibility versus its diameter. It was hypothesized that a) sympathetic activation and nitric oxide competitively impact muscular conduit artery (brachial artery) mechanics, and b) neurogenic constrictor input affects conduit vessel stiffness independent of outright changes in conduit vessel diastolic diameter. Lower body negative pressure (LBNP) and a cold pressor stress (CPT) were used to study the changes in conduit vessel mechanics when the increased sympathetic outflow occurred with and without changes in heart rate (LBNP -40 vs. -15 mmHg) and blood pressure (CPT vs. LBNP). These manoeuvres were performed in the absence and presence of nitroglycerin (NG). Neither LBNP nor CPT altered brachial artery diastolic diameter; however, distensibility was reduced by 25% - 54% in each reflex (all p < 0.05). This impact of sympathetic activation on brachial artery distensibility was not altered by NG supplementation (21 -54%; p<0.05), although baseline diameter was increased by the exogenous nitric oxide (p<0.05). The results indicate that sympathetic excitation can reduce the distensibility of the brachial artery independently of concurrent changes in diastolic diameter, heart rate and blood pressure. However, exogenous nitric oxide did not minimize or reverse brachial stiffening during sympathetic activation. Therefore, sympathetic outflow appears to impact the stiffness of this conduit vessel rather than its diastolic diameter or, by inference, its local resistance to flow.