Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients

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.

Role of nitric oxide in vasovagal syncope. A puzzle solved but there could be another piece

“…It can be inferred that reactivity to nitrates increases with the presence of TNF leading to vasodilation. The results of Stewart et al 1 are encouraging for clinical practice as we agree with the authors that there could be a role for NO modulation in the treatment of this common disease.…”

“…Stewart et al 1 reported a very ingenious study that finally demonstrated the previously controversial role of nitric oxide (NO) in vasovagal syncope (VVS). They used a different approach that certainly explains that they have obtained positive findings.…”

Mechanisms of tilt‐induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope

“…We also showed that inhibiting NO synthesis increased adrenergic vasoconstriction, increased SVR and splanchnic vasodilation, and normalized orthostatic tolerance in young patients with VVS (Stewart et al. , ). Blood flow and vascular resistance responses to orthostatic stress in our current Control‐Faint group were similar to those found previously in recurrent VVS patients, findings caused exclusively by decreased SVR.…”

Current Concepts of Pathophysiology of Vasovagal Syncope and its Evaluation and Management: A Review

“…B u t i f N O i n d u c e d vasodilation overcomes the adrenergic vasoconstrictor effect, the resulting vasodilation will contribute to a possible VVS. That this happens in young adults with recurrent VVS was elegantly demonstrated by Stewart et al (74). They concluded that in patients with recurrent VVS, there is large scale vasodilation, particularly in the splanchnic bed which is mediated by NO which is secreted by neuronal NO via nitrergic nerves, a nomenclature suggested by Toda et al (75) to describe neuronal N O s y n t h e s i z e d i n p o s t g a n g l i o n i c parasympathetic nerves to distinguish them from cholinergic nerves.…”

“…The role of NO in causing vasodilation during VVS has been elaborated earlier (74)(75)(76). In fact, Stewart et al (74) demonstrated that use of NO synthase inhibitors was helpful in attenuating the vasodilation during of VVS and is deemed promising as a tool for use in patients of recurrent VVS.…”