title: NO synthase blockade induces chaotic cerebral vasomotion via activation of thromboxane receptors.
abstract: OBJECTIVE
  Instability of the vascular tone (vasomotion) develops in several cerebrovascular diseases associated with endothelial dysfunction. The aim of the present study was to characterize cerebral vasomotion induced by diminished NO production with quantitative evaluation and chaos analysis. We tested the hypothesis that activation of thromboxane receptors mediates chaotic vasomotion after NO synthase (NOS) inhibition.
  
  
  METHODS
  Measurements of vascular tension were carried out in isolated rat middle cerebral arteries. The extent of vasomotion was characterized by tension instability, whereas vasomotion complexity was assessed by chaos analysis.
  
  
  RESULTS
  Blocking the basal NO release by N(omega)-nitro-L-arginine (L-NA) induced vasomotion, which was further enhanced and became irregular after UTP administration. The NO donor sodium nitroprusside was able to reverse this effect, and stable steady-state conditions reappeared. The guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) or coapplication of ODQ and L-NA had an effect identical to that of L-NA alone. Vasoconstriction by K(+) failed to induce vasomotion in intact vessels or in the presence of L-NA or ODQ. The thromboxane receptor antagonist ICI 192605 dose-dependently attenuated the vasomotion induced by L-NA and UTP, and the thromboxane-receptor agonist U-46619 induced significant vasomotion in intact vessels.
  
  
  CONCLUSIONS
  The lack of NO in cerebral vessels provokes vulnerability to chaotic vasomotion, which can be triggered by the administration of UTP, whereas excess NO reverses it to stable conditions. The vasomotion after blockade of the NO-cGMP pathway is mediated by activation of thromboxane receptors.
authors.affiliation: Department of Physiology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Lacza
authors.forename: P
authors.initials: P
authors.lastname: Hermán
authors.forename: C
authors.initials: C
authors.lastname: Görlach
authors.forename: T
authors.initials: T
authors.lastname: Hortobágyi
authors.forename: P
authors.initials: P
authors.lastname: Sándor
authors.forename: M
authors.initials: M
authors.lastname: Wahl
authors.forename: Z
authors.initials: Z
authors.lastname: Benyó
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D020768:Middle Cerebral Artery / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D017711:Nonlinear Dynamics; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000378:metabolism*; D014661:Vasoconstriction; D014666:Vasomotor System / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D017482:Receptors, Thromboxane; D019335:Nitroarginine; D019001:Nitric Oxide Synthase