Heart and Circulatory Physiology

Cutaneous constitutive nitric oxide synthase activation in postural tachycardia syndrome with splanchnic hyperemia

Julian M. Stewart, Abhinav Nafday, Anthony J. Ocon, Courtney Terilli, Marvin S. Medow


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-Nω-nitroarginine-2,4-l-diamino-butyric amide (Nω, 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 (%CVCmax) in POTS compared with 88 ± 2%CVCmax in control subjects but decreased to the same level with Nω (46 ± 5%CVCmax in POTS compared with 49 ± 4%CVCmax in control) or with NLA (45 ± 3%CVCmax in POTS compared with 47 ± 4%CVCmax 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.

  • nitric oxide synthase isoforms
  • laser-Doppler flowmetry
  • acetylcholine
  • cutaneous blood flow
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