B1 kinin receptor activity in pigs is associated with pre-existing infection

Immunopharmacology. 1998 Jul;40(1):49-55. doi: 10.1016/s0162-3109(98)00035-6.

Abstract

Bradykinin (BK) and related kinins are potent inflammatory mediators produced during acute and chronic inflammation. The effects of these kinins are mediated via the stimulation of either a B2 or a B1 receptor. The B1 receptor is not normally present but its expression can be induced within 4 h by a variety of noxious stimuli, specifically, gram-negative bacteria or bacterial lipopolysaccharide (LPS) given to healthy animals. This study compared the cardiovascular response of healthy pigs and pigs diagnosed with a pre-existing spontaneously acquired infection to BK, a B2 receptor agonist, and des-Arg9-BK, a B1 receptor agonist. Eighty-eight percent of the animals diagnosed with an established infection based on a standardized clinical evaluation demonstrated increased sensitivity and responsiveness to des-Arg9-BK but normal responsiveness to BK and acetylcholine. In contrast, only 15% of healthy animals showed elevated responses to des-Arg9-BK. The response to des-Arg9-BK and BK in each group was characterised as B1 and B2, respectively, using the selective B1 and B2 antagonists Lys0-Leu8-des-Arg9-BK and Hoe 140, respectively. This study demonstrates the existence and function of the B1 receptor in animals with a previously acquired infection. These observations lend validity to animal experiments with LPS infusion in order to model bacterial inflammation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Bacterial Infections / etiology
  • Bacterial Infections / metabolism*
  • Blood Pressure / drug effects
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists
  • Gram-Negative Bacteria
  • Heart Rate / drug effects
  • Lipopolysaccharides
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / agonists*
  • Swine

Substances

  • Bradykinin Receptor Antagonists
  • Lipopolysaccharides
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • bradykinin, des-Arg(9)-
  • bradykinin, Leu(8)-des-Arg(9)-
  • icatibant
  • Acetylcholine
  • Bradykinin