Monophosphoryl lipid A, a derivative of bacterial lipopolysaccharide, fails to induce B-1-receptor-dependenr responses to (des-Arg(9))-bradykinin in the rabbit in vivo

Objective. The aim of this study was to evaluate whether monophosphoryl lip id A (MLA) was able to induce a hypotensive response to (des-Arg(9))-bradyk inin in the rabbit in vivo, by inducing B-1-receptor synthesis. Materials a nd methods. Arterial pressure was measured after intra-arterial administrat ion of B-1- and B-2-receptor agonists and antagonists in control rabbits an d in rabbits pre-treated 24 h earlier with MLA (100 mu g kg(-1) i.v.) or li popolysaccharide (LPS) (10 mu g kg(-1) i.v.). Results. Intra-arterial brady kinin administration induced a similar dose-dependent hypotension in all gr oups (BK 0.25 mu g kg(-1), 36 +/- 3 mm Hg, BK 1 mu g kg(-1), - 39 +/- 3 mm Hg, p < 0.05 vs. control conditions) that was significantly antagonised by intra-arterial HOE 140 (2 mu g kg(-1)) (-5 +/- 2 mm Hg, p < 0.05). Intra-ar terial (des-Arg(9))-bradykinin induced a hypotensive response in the LPS-pr e-treated group (DBK 1 mu g kg(-1) -6+/-1 mm Hg, DBK 10 mu g kg(-1) -10 +/- 1 mm Hg, p < 0.05 vs. control conditions) that was totally abolished by in tra-arterial (des-Arg(9), Leu(8))-bradykinin (10 mu g kg(-1) min(-1)) (+ 1 +/- 2 mm Hg, p < 0.05). In the control and MLA-pre-treated groups, (des-Arg (9))-bradykinin had no effect. Conclusion. MLA pre-treatment did not induce a hypotensive response to (des-Arg(9))-bradykinin. We conclude that, in co ntrast to LPS, MLA does not induce B-1-receptor synthesis, 24 h after its a dministration in the rabbit. Thus, the cardioprotective effects of MLA do n ot appear to be related to the kinin pathway. (C) 1999 Elsevier Science B.V . All rights reserved.