B-1 KININ RECEPTOR ACTIVITY IN PIGS IS ASSOCIATED WITH PREEXISTING INFECTION

Bradykinin (BK) and related kinins are potent inflammatory mediators p roduced during acute and chronic inflammation. The effects of these ki nins are mediated via the stimulation of either a B-2 or a B-1 recepto r. The B-1 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 heal thy animals. This study compared the cardiovascular response of health y pigs and pigs diagnosed with a pre-existing spontaneously acquired i nfection to BK, a B-2 receptor agonist, and des-Arg(9)-BK, a B-1 recep tor agonist. Eighty-eight percent of the animals diagnosed with an est ablished infection based on a standardized clinical evaluation demonst rated increased sensitivity and responsiveness to des-Arg(9)-BK but no rmal responsiveness to BK and acetylcholine. In contrast, only 15% of healthy animals showed elevated responses to des-Arg(9)-BK. The respon se to des-Arg(9)-BK and BK in each group was characterised as B-1 and B-2, respectively, using the selective B-1 and B-2 antagonists Lys(0)- Leu(8)-des-Arg(9)-BK and Hoe 140, respectively. This study demonstrate s the existence and function of the B-1 receptor in animals with a pre viously acquired infection. These observations lend validity to animal experiments with LPS infusion in order to model bacterial inflammatio n. (C) 1998 Elsevier Science B.V. All rights reserved.