title: Role of sensory neuron in reduction of endotoxin-induced hypotension in rats.
abstract: OBJECTIVE
  We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats.
  
  
  METHODS
  Prospective, randomized, controlled study.
  
  
  METHODS
  Research laboratory at a university medical center.
  
  
  METHODS
  Wistar rats weighing 220-280 g.
  
  
  METHODS
  Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F1alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2/NO3 was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F1alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F1alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 +/- 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and iNOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (1 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response.
  
  
  CONCLUSIONS
  Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin.
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Isobe
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Uchiba
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D002211:Capsaicin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism*; D016285:Iloprost / Q000633:toxicity; D007213:Indomethacin / Q000008:administration & dosage*; D019410:Interleukin-16 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014665:Vasodilator Agents / Q000633:toxicity
chemical_list: D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D019410:Interleukin-16; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D016285:Iloprost; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; D007213:Indomethacin