Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome.
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 on subjects aged 22.5 +/- 2 yr. We used laser-Doppler flowmetry response to sequentially increase acetylcholine (ACh) doses and the local cutaneous heating response of the calf as bioassays for NO. During local heating we showed that when the selective neuronal nNO synthase (nNOS) inhibitor N(omega)-nitro-L-arginine-2,4-L-diaminobutyric amide (N(omega), 10 mM) was delivered by intradermal microdialysis, cutaneous vascular conductance (CVC) decreased by an amount equivalent to the largest reduction produced by the nonselective NO synthase (NOS) inhibitor nitro-L-arginine (NLA, 10 mM). We demonstrated that the response to ACh was minimally attenuated by nNOS blockade using N(omega) but markedly attenuated by NLA, indicating that eNO largely comprises the receptor-mediated NO release by ACh. We further demonstrated that the ACh dose response was minimally reduced, whereas local heat-mediated NO-dependent responses were markedly reduced in POTS compared with 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 percent maximum CVC(%CVC(max))] compared with control (90 +/- 4 %CVC(max)), but the plateau response decreased to the same level with nNOS inhibition (50 +/- 3 %CVC(max) in POTS compared with 47 +/- 2 %CVC(max)), indicating reduced nNO bioavailability in POTS patients. The data suggest that nNO activity but not NO of endothelial NOS origin is reduced in low-flow POTS.
The Center for Pediatric Hypotension, New York Medical College, Ste. 3050, 19 Bradhurst Ave., Hawthorne, NY 10532, USA. stewart@nymc.edu
Julian M
JM
Stewart
Marvin S
MS
Medow
Christopher T
CT
Minson
Indu
I
Taneja
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation / Q000294:innervation; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; 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*; D019335:Nitroarginine / Q000494:pharmacology; D011187:Posture; D012039:Regional Blood Flow; D012107:Research Design; D012867:Skin / Q000098:blood supply*; D013577:Syndrome; D013610:Tachycardia / Q000378:metabolism* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; C120839:N(omega)-nitroarginine-2,4-diaminobutryic amide; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine