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Original research article
Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients
  1. Julian M Stewart1,2,
  2. Richard Sutton3,
  3. Mira L Kothari1,
  4. Amanda M Goetz1,
  5. Paul Visintainer4,
  6. Marvin Scott Medow1,2
  1. 1 Departments of Pediatrics, New York Medical College, Valhalla, New York, USA
  2. 2 Departments of Physiology, New York Medical College, Valhalla, New York, USA
  3. 3 The National Heart & Lung Institute, Imperial College, London, UK
  4. 4 Baystate Medical Center, University of Massachusetts School of Medicine 4, Springfield MA, USA
  1. Correspondence to Professor Julian M Stewart, New York Medical College, Center for Hypotension 19 Bradhurst Ave, Suite 1600S, Hawthorne, New York 10532; julian_stewart{at}nymc.edu

Abstract

Objective Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients.

Methods We recorded haemodynamics in supine VVS and healthy volunteers (aged 15–27 years), challenged with graded lower body negative pressure (LBNP) (−15, –30, −45 mm Hg each for 5 min, then −60 mm Hg for a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA.

Results Controls endured 25.9±4.0 min of LBNP during Saline+PE compared with 11.6±1.4 min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2 min compared with 22.6±1.6 min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored.

Conclusions We conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide.

  • vascular biology
  • pharmacology
  • neurologic events

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Footnotes

  • Contributors JMS was responsible for the conception and design of the experiments, interpretation of data and drafting the article. RS was responsible for interpretation of the data and revising the manuscript. MLK was responsible for collection, assembly and interpretation of the data. AMG was responsible for collection, assembly and interpretation of the data. PV was responsible for biostatistical analysis and interpretation of the data and critically revising intellectual content of the article. MSM was responsible for design of the experiments, analysis and interpretation of the data and critically revising intellectual content of the article. All authors read and approved the final article.

  • Funding Funding for this project was provided by National Institutes of Health grant RO1 HL 112736 (JMS) and NIH R21NS 094644 (MSM).

  • Competing interests None declared.

  • Patient consent Consent for our research were signed by patient, and by guardian if under 18 years old. However, the data presented here are completely anonymized.

  • Ethics approval Committee for the Protection of Human Subjects of New York Medical College.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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