Lipopolysaccharide decreases bradykinin receptor-induced acidification responses in cultured bovine aortic endothelial cells

The effects of bacterial Lipopolysaccharide (Escherichia coli 0127-B8) on b radykinin receptor function in bovine aortic endothelial cells were investi gated using a microphysiometer. Bradykinin and Lys(0)-desArg(10)-bradykinin produced concentration-dependent acidification responses with pEC(50) valu es of 8.87 +/- 0.20 and 9.78 +/- 0.08, respectively. These responses were c ompetitively and selectively antagonised by the bradykinin B-2 receptor ant agonist, icatibant and the bradykinin B-1 receptor antagonist, desArg(9)-Le u(8)-bradykinin, respectively. The non-peptide bradykinin B-2 receptor anta gonist, FR173657 (0.3 and 3 nM), selectively antagonised bradykinin-induced acidification responses, causing rightward shifts of the concentration-res ponse curves to bradykinin, but at the same time, significantly decreasing the maximum response. A preincubation with lipopolysaccharide (0.01 and 0.1 mu g/ml) for 24 h caused a significant concentration-dependent decrease in maximal response to bradykinin (27.2 +/- 1.9 and 9.7 +/- 0.4% of control) and the bradykinin B-1 receptor agonist, Lys(0)-desArg(10)-bradykinin (59.0 +/- 7.14 and 25.3 +/- 7.8% of control), without affecting the EC50. These results suggest that bradykinin B-1 receptors are constitutively expressed in cultured bovine aortic endothelial cells and that the microphysiometer p rovides a rapid, sensitive technique to characterise bradykinin receptors a nd investigate their regulation by cytokines. Interactions between bradykin in receptors and lipopolysaccharide may play a part in the cascade of delet erious effects that occur during septic shock. (C) 2000 Elsevier Science B. V. All rights reserved.