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Open Access Research

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

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-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.

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.

Conclusion

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

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