Low flow postural tachycardia syndrome (POTS), is associated with increased plasma angiotensin-II (Ang-II) and reduced neuronal nitric oxide (NO) which decreases NO-dependent vasodilation. We tested whether the angiotensin-II type 1 receptor antagonist losartan would improve NO-dependent vasodilation in these POTS patients. Further if the action of Ang-II is dependent on NO, then the NOS inhibitor nitro-L-arginine (NLA) would reverse this improvement. We used local heating of the skin of the left calf to 42°C and laser Doppler Flowmetry to assess NO-dependent conductance (%CVC_max) in 12 low flow POTS patients aged 22.5±.8 years and in 15 control subjects aged 22.0±1.3 years. After measuring the baseline local heating response at 3 separate sites, we perfused individual intradermal microdialysis catheters at those sites with losartan 2µg/L, or NLA 10mM, or losartan + NLA. The pre-drug heat response was reduced in POTS, particularly the plateau phase reflecting NO-dependent vasodilation (50±5 vs 91±7 %CVC_max, P<.001 vs control). Losartan increased baseline flow in both POTS and control subjects (from 6±1 to 21±3 vs from 10±1 to 21±2, P<0.05 compared to pre-drug). The baseline increase was blunted by NLA. Losartan increased the POTS heat response to equal the control subject response (79±7 vs 88±6, P=.48). NLA decreased both POTS and control subject heat responses to similar conductances (38±4 vs 38±3, P<.05 compared to pre-drug). The addition of NLA to losartan reduced POTS and control subject conductances compared to losartan alone (48±3 vs 53±2). The data suggest that the reduction in cutaneous nitric oxide dependent vasodilation in low flow POTS is corrected by AT1R blockade.