title: Cutaneous constitutive nitric oxide synthase activation in postural tachycardia syndrome with splanchnic hyperemia.
abstract: Models of microgravity are linked to excessive constitutive nitric oxide (NO) synthase (NOS), splanchnic vasodilation, and orthostatic intolerance. Normal-flow postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance associated with splanchnic hyperemia. To test the hypothesis that there is excessive constitutive NOS in POTS, we determined whether cutaneous microvascular neuronal NO and endothelial NO are increased. We performed two sets of experiments in POTS and control subjects aged 21.4 ± 2 yr. We used laser-Doppler flowmetry to measure the cutaneous response to local heating as an indicator of bioavailable neuronal NO. To test for bioavailable endothelial NO, we infused intradermal acetylcholine through intradermal microdialysis catheters and used the selective neuronal NOS inhibitor l-N(ω)-nitroarginine-2,4-L-diamino-butyric amide (N(ω), 10 mM), the selective inducible NOS inhibitor aminoguanidine (10 mM), the nonspecific NOS inhibitor nitro-l-arginine (NLA, 10 mM), or Ringer solution. The acetylcholine dose response and the NO-dependent plateau of the local heating response were increased in POTS compared with those in control subjects. The local heating plateau was significantly higher, 98 ± 1%maximum cutaneous vascular conductance (%CVC(max)) in POTS compared with 88 ± 2%CVC(max) in control subjects but decreased to the same level with N(ω) (46 ± 5%CVC(max) in POTS compared with 49 ± 4%CVC(max) in control) or with NLA (45 ± 3%CVC(max) in POTS compared with 47 ± 4%CVC(max) in control). Only NLA blunted the acetylcholine dose response, indicating that NO produced by endothelial NOS was released by acetylcholine. Aminoguanidine was without effect. This is consistent with increased endothelial and neuronal NOS activity in normal-flow POTS.
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York, New York, USA. julian_stewart@nymc.edu
authors.forename: Julian M
authors.initials: JM
authors.lastname: Stewart
authors.forename: Abhinav
authors.initials: A
authors.lastname: Nafday
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Ocon
authors.forename: Courtney
authors.initials: C
authors.lastname: Terilli
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Medow
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000201:enzymology* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017551:Microdialysis; D055806:Microvessels / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054972:Postural Orthostatic Tachycardia Syndrome / Q000201:enzymology* / Q000503:physiopathology; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature; D013152:Splanchnic Circulation; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III