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Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat

Sébastien Talbot, Helaine De Brito Gariépy, Julien Saint-Denis and Réjean Couture*

Author Affiliations

Department of Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Downtown, Montréal, QC H3C 3J7, Canada

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Journal of Neuroinflammation 2012, 9:214  doi:10.1186/1742-2094-9-214

Published: 13 September 2012



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.


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-Arg9-Bradykinin (BK) and Sar-[D-Phe8]des-Arg9-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.


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.


B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2) and nitric oxide.

Kinin B1 receptor; Diabetes; Hyperthermia; Inflammation; Bradykinin; NO; Sensory C-fibers; Thermoregulation