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Development of hyperthermia following intracerebroventricular administration of endotoxin in the rat: effect of kinin B 1 and B 2 receptor antagonists
Author(s) -
Walker Katharine,
Dray Andy,
Perkins Martin
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15244.x
Subject(s) - hyperthermia , bradykinin , antagonist , receptor antagonist , lipopolysaccharide , kinin , receptor , endocrinology , medicine , chemistry , pharmacology , systemic administration , bradykinin receptor , biology , in vivo , microbiology and biotechnology
1 E. coli lipopolysaccharide (LPS) produced a dose‐dependent (dose range: 0.02–150 μg) increase in rat core temperature that was maximal 6 h after intracerebroventricular (i.c.v.) administration. LPS (200 ng) increased core temperature by 1.0±0.2°C, 6 h following administration, as compared to vehicle‐treated controls (−0.2±0.2°C). 2 LPS‐induced (200 ng) hyperthermia was prevented by co‐administration of the bradykinin (BK) B 2 receptor antagonist, Hoe 140 (10 and 30 pmol, i.c.v.) or by indomethacin (10 nmol, i.c.v.). 3 Systemic administration of Hoe 140 at doses up to 1 μmol kg −1 , s.c., did not attenuate LPS‐induced (200 ng, i.c.v.) hyperthermia. However, LPS hyperthermia was significantly reduced by systemic administration of indomethacin (1 μmol kg −1 , i.v.). 4 Co‐administration of the selective B 1 receptor antagonists, [des‐Arg 9 , Leu 8 ]BK (0.1‐1 nmol, i.c.v.) or [des‐Arg 10 ] Hoe 140 (0.1‐1 nmol, i.c.v.), did not prevent LPS‐induced hyperthermia. 5 It is concluded that the development of hyperthermia following central administration of endotoxin requires activation of central, but not peripheral bradykinin B 2 receptors. The formation of kinins within the CNS may be an important initial component of CNS inflammation following infection.