title: Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat.
abstract: BACKGROUND
  Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R.
  
  
  METHODS
  Male Sprague-Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p.) to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg) of des-Arg(9)-Bradykinin (BK) and Sar-[D-Phe(8)]des-Arg(9)-BK (B1R agonists) or BK (B2R agonist). The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR) and B1R was localized by confocal microscopy.
  
  
  RESULTS
  B1R agonists (0.1 to 5 mg/kg) showed transient (5- to 30-minute) and dose-dependent increases of rectal temperature (+1.5°C) in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612), cyclooxygenase-2 (COX-2) (niflumic acid) and nitric oxide synthase (NOS) (L-NAME), and after vagal nerve ligation. In contrast, COX-1 inhibition (indomethacin) had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers.
  
  
  CONCLUSIONS
  B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2) and nitric oxide.
authors.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Talbot
authors.forename: Helaine
authors.initials: H
authors.lastname: De Brito Gariépy
authors.forename: Julien
authors.initials: J
authors.lastname: Saint-Denis
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D001920:Bradykinin