title: Low voltage vagal nerve stimulation reduces bronchoconstriction in guinea pigs through catecholamine release.
abstract: OBJECTIVE
  Electrical stimulation of the vagus nerve at relatively high voltages (e.g., >10 V) can induce bronchoconstriction. However, low voltage (≤2 V) vagus nerve stimulation (VNS) can attenuate histamine-invoked bronchoconstriction. Here, we identify the mechanism for this inhibition.
  
  
  METHODS
  In urethanea-nesthetized guinea pigs, bipolar electrodes were attached to both vagus nerves and changes in pulmonary inflation pressure were recorded in response to i.v. histamine and during VNS. The attenuation of the histamine response by low-voltage VNS was then examined in the presence of pharmacologic inhibitors or nerve ligation.
  
  
  RESULTS
  Low-voltage VNS attenuated histamine-induced bronchoconstriction (4.4 ± 0.3 vs. 3.2 ± 0.2 cm H(2) O, p < 0.01) and remained effective following administration of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, and after sympathetic nerve depletion with guanethidine, but not after the β-adrenoceptor antagonist propranolol. Nerve ligation caudal to the electrodes did not block the inhibition but cephalic nerve ligation did. Low-voltage VNS increased circulating epinephrine and norepinephrine without but not with cephalic nerve ligation.
  
  
  CONCLUSIONS
  These results indicate that low-voltage VNS attenuates histamine-induced bronchoconstriction via activation of afferent nerves, resulting in a systemic increase in catecholamines likely arising from the adrenal medulla.
authors.affiliation: ElectroCore LLC, Morris Plains, NJ, USA; and             Department of Anesthesiology, Columbia University, New York, NY, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Simon
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000097:blood; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008026:Ligation / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D002395:Catecholamines; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D006632:Histamine; D011433:Propranolol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D004837:Epinephrine; D006145:Guanethidine