Nitric Oxide Synthase Inhibition Restores Orthostatic Tolerance in Young Vasovagal Syncope Patients
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.
Stewart, J., Sutton, R., Kothari, M., Goetz, A., Visintainer, P., & Medow, M. (2017). Nitric Oxide Synthase Inhibition Restores Orthostatic Tolerance in Young Vasovagal Syncope Patients. Heart (British Cardiac Society), 103 (21), 1711-1718. https://doi.org/10.1136/heartjnl-2017-311161