icatibant and Bacterial-Infections

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.

Topics: Acetylcholine; Animals; Bacterial Infections; Blood Pressure; Bradykinin; Bradykinin Receptor Antagonists; Gram-Negative Bacteria; Heart Rate; Lipopolysaccharides; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Receptors, Bradykinin; Swine