Postsynaptic α 1 -Adrenergic Vasoconstriction Is Impaired in Young Patients With Vasovagal Syncope and Is Corrected by Nitric Oxide Synthase Inhibition

Abstract

Background— Syncope is a sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). During VVS, gravitational pooling excessively reduces central blood volume and cardiac output. In VVS, as in hemorrhage, impaired adrenergic vasoconstriction and venoconstriction result in hypotension. We hypothesized that impaired adrenergic responsiveness because of excess nitric oxide can be reversed by reducing nitric oxide. Methods and Results— We recorded cardiopulmonary dynamics in supine syncope patients and healthy volunteers (aged 15–27 years) challenged with a dose–response using the α 1 -agonist phenylephrine (PE), with and without the nitric oxide synthase inhibitor N G -monomethyl- L -arginine, monoacetate salt (L-NMMA). Systolic and diastolic pressures among control and VVS were the same, although they increased after L-NMMA and saline+PE (volume and pressor control for L-NMMA). Heart rate was significantly reduced by L-NMMA ( P <0.05) for control and VVS compared with baseline, but there was no significant difference in heart rate between L-NMMA and saline+PE. Cardiac output and splanchnic blood flow were reduced by L-NMMA for control and VVS ( P <0.05) compared with baseline, while total peripheral resistance increased ( P <0.05). PE dose–response for splanchnic flow and resistance were blunted for VVS compared with control after saline+PE, but enhanced after L-NMMA ( P <0.001). Postsynaptic α 1 -adrenergic vasoconstrictive impairment was greatest in the splanchnic vasculature, and splanchnic blood flow was unaffected by PE. Forearm and calf α 1 -adrenergic vasoconstriction were unimpaired in VVS and unaffected by L-NMMA. Conclusions— Impaired postsynaptic α 1 -adrenergic vasoconstriction in young adults with VVS can be corrected by nitric oxide synthase inhibition, demonstrated with our use of L-NMMA.