Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome

Abstract

Stewart JM, Taneja I, Glover J, Medow MS. Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol 294: H466–H473, 2008. First published November 9, 2007; doi:10.1152/ajpheart.01139.2007.—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 ANG II type 1 receptor (AT1R) antagonist losartan would improve NO-dependent vasodilation in POTS patients. Furthermore, if the action of ANG II is dependent on NO, then the NO synthase 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 [percent maximum cutaneous vascular conductance (%CVCmax)] in 12 low-flow POTS patients aged 22.5 0.8 yr and in 15 control subjects aged 22.0 1.3 yr. After measuring the baseline local heating response at three separate sites, we perfused individual intradermal microdialysis catheters at those sites with 2 g/l losartan, 10 mM NLA, or losartan NLA. The predrug heat response was reduced in POTS, particularly the plateau phase reflecting NO-dependent vasodilation (50 5 vs. 91 7 %CVCmax; P 0.001 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 %CVCmax; P 0.05 compared with predrug). The baseline increase was blunted by NLA. Losartan increased the POTS heat response to equal the control subject response (79 7 vs. 88 6 %CVCmax; P 0.48). NLA decreased both POTS and control subject heat responses to similar conductances (38 4 vs. 38 3 %CVCmax; P 0.05 compared with predrug). The addition of NLA to losartan reduced POTS and control subject conductances compared with losartan alone (48 3 vs. 53 2 %CVCmax). The data suggest that the reduction in cutaneous NO-dependent vasodilation in low-flow POTS is corrected by AT1R blockade.