B1 kinin receptor activity in pigs is associated with pre-existing infection.
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.
Siebeck
M
M
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians University, Munich, Germany. m.siebeck@lrz.uni-muenchen.de
Schorr
M
M
Spannagl
E
E
Lehner
M
M
Fritz
H
H
Cheronis
J C
JC
Whalley
E T
ET
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D006090:Gram-Negative Bacteria; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists*; D013552:Swine
D065168:Bradykinin Receptor Antagonists; D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D000109:Acetylcholine; D001920:Bradykinin