title: Postsynaptic α1-Adrenergic Vasoconstriction Is Impaired in Young Patients With Vasovagal Syncope and Is Corrected by Nitric Oxide Synthase Inhibition.
abstract: 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.
  
  
  
  We recorded cardiopulmonary dynamics in supine syncope patients and healthy volunteers (aged 15-27 years) challenged with a dose-response using the α1-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 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.
  
  
  
  Impaired postsynaptic α1-adrenergic vasoconstriction in young adults with VVS can be corrected by nitric oxide synthase inhibition, demonstrated with our use of L-NMMA.
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.). julian_stewart@nymc.edu marvin_medow@nymc.edu.
authors.forename: Julian M
authors.initials: JM
authors.lastname: Stewart
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.).
authors.forename: Melissa
authors.initials: M
authors.lastname: Suggs
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.).
authors.forename: Sana
authors.initials: S
authors.lastname: Merchant
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.).
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.).
authors.forename: Courtney
authors.initials: C
authors.lastname: Terilli
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.).
authors.forename: Paul
authors.initials: P
authors.lastname: Visintainer
authors.affiliation: From the Departments of Pediatrics (J.M.S., S.M., C.T., M.S.M.), Physiology (J.M.S., M.S., M.S.M.), New York Medical College, Valhalla, NY; The National Heart & Lung Institute, Imperial College, London, United Kingdom (R.S.); and Department of Medicine, Baystate Medical Center, Springfield & Tufts University School of Medicine, MA (P.V.). julian_stewart@nymc.edu marvin_medow@nymc.edu.
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Medow
mesh_terms: D000293:Adolescent; D000328:Adult; D002302:Cardiac Output / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D013152:Splanchnic Circulation / Q000187:drug effects; D019462:Syncope, Vasovagal / Q000188:drug therapy* / Q000201:enzymology*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase
keywords: L-NMMA; adrenergic regulation; dose–response; nitric oxide; nitric oxide synthase; phenylephrine; syncope (fainting)