title: Ascorbate improves circulation in postural tachycardia syndrome.
abstract: Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10532, USA. julian_stewart@nymc.edu
authors.forename: Julian M
authors.initials: JM
authors.lastname: Stewart
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Ocon
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Medow
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D001775:Blood Circulation / Q000187:drug effects*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D007866:Leg / Q000098:blood supply*; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D054972:Postural Orthostatic Tachycardia Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D016896:Treatment Outcome; D018924:Vascular Capacitance / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D055815:Young Adult
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D001205:Ascorbic Acid