NYMC Faculty Publications

Title

Nitric Oxide Synthase Inhibition Restores Orthostatic Tolerance in Young Vasovagal Syncope Patients

Document Type

Article

Publication Date

11-1-2017

Department

Pediatrics

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 patientswas 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.

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