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1 Pediatrics and Physiology, New York Medical College, Valhalla, New York, United States
2 Department of Human Physiology, University of Oregon, Eugene, Oregon, United States
3 Pediatrics and Medicine, New York Medical College, Valhalla, New York, United States
* To whom correspondence should be addressed. E-mail: julian_stewart{at}nymc.edu.
Low flow postural tachycardia syndrome (POTS), is associated with reduced nitric oxide (NO) activity assumed to be of endothelial origin.
We tested the hypothesis that cutaneous microvascular neuronal NO (nNO) is impaired rather than endothelial NO (eNO) in POTS. We performed three sets of experiments in subjects aged 22.5±2 years. We used laser Doppler flowmetry response to sequentially increase acetylcholine doses and to the local cutaneous heating response of the calf as bioassays for NO. First, during local heating we showed that when the selective neuronal nitric oxide synthase (NOS) inhibitor L-N
-Nitroarginine-2,4-L-diamino-butyric amide (N
, 10 mM) was delivered by intradermal microdialysis, cutaneous vascular conductance decreased by an amount equivalent to the largest reduction produced by the nonselective NOS inhibitor nitro-L-arginine (NLA 10mM). Second, we demonstrated that the response to acetylcholine was minimally attenuated by nNOS blockade using N
, but markedly attenuated by NLA, indicating that eNO largely comprises the receptor mediated NO release by acetylcholine. Third, we demonstrated that the acetylcholine dose-response was minimally reduced while local heat mediated NO-dependent responses were markedly reduced in POTS compared to control subjects. This is consistent with intact endothelial function and reduced NO of neuronal origin in POTS. The local heating response was highly attenuated in POTS (60±6 %CVCmax) compared to control (90±4 %CVCmax), but the plateau response decreased to the same level with nNOS inhibition (50±3 %CVCmax in POTS compared to 47±2 %CVCmax) indicating reduced nNO bioavailability in POTS patients.
The data suggest that neuronal nitric oxide activity, but not nitric oxide of eNOS origin, is reduced in low flow POTS.
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