Orthostasis in VVS is accompanied by large increases in HR that should not be construed as POTS.

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 due to excess nitric oxide (NO) can be reversed by reducing NO. Methods and Results We recorded cardio-pulmonary dynamics in supine syncope patients and healthy volunteers, (ages 15–27) challenged with a dose-response (DR) using the α1- agonist phenylephrine (PE), with and without the NO synthase inhibitor L-NMMA. Systolic and diastolic pressures among control and VVS were the same, although increased after L-NMMA and Saline+PE (volume and pressor control for L-NMMA). HR was significantly reduced by L-NMMA (P<0.05) for control and VVS compared to baseline but there was no significant difference in HR 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 to baseline while total peripheral resistance (TPR) increased (P<0.05). Phenylephrine DR for splanchnic flow and resistance were blunted for VVS compared to control after Saline+PE, but enhanced after L-NMMA (P<0.001). Post-synaptic α1-adrenergic vasoconstrictive impairment was greatest in the splanchnic vasculature, and splanchnic blood flow was unaffected by PE. Forearm and calf α1-adrenergic vasoconstriction were unimpaired in VVS and unaffected by L-NMMA. Conclusions Impaired post-synaptic α1-adrenergic vasoconstriction in young adults with VVS can be corrected by NO synthase inhibition, demonstrated with our use of L-NMMA.