Monophosphoryl lipid A, a derivative of bacterial lipopolysaccharide, fails to induce B1-receptor-dependent responses to (des-Arg9)-bradykinin in the rabbit in vivo.

OBJECTIVE

The aim of this study was to evaluate whether monophosphoryl lipid A (MLA) was able to induce a hypotensive response to (des-Arg9)-bradykinin in the rabbit in vivo, by inducing B1-receptor synthesis.

MATERIALS AND METHODS

Arterial pressure was measured after intra-arterial administration of B1- and B2-receptor agonists and antagonists in control rabbits and in rabbits pre-treated 24 h earlier with MLA (100 microg kg(-1) i.v.) or lipopolysaccharide (LPS) (10 microg kg(-1) i.v.).

RESULTS

Intra-arterial bradykinin administration induced a similar dose-dependent hypotension in all groups (BK 0.25 microg kg(-1), 36 +/- 3 mm Hg, BK 1 microg kg(-1), -39 +/- 3 mm Hg, p < 0.05 vs. control conditions) that was significantly antagonised by intra-arterial HOE 140 (2 microg kg(-1)) (-5 +/- 2 mm Hg, p < 0.05). Intra-arterial (des-Arg9)-bradykinin induced a hypotensive response in the LPS-pre-treated group (DBK 1 microg kg(-1), -6 +/- 1 mm Hg, DBK 10 microg kg(-1), -10 +/- 1 mm Hg, p < 0.05 vs. control conditions) that was totally abolished by intra-arterial (des-Arg9, Leu8)-bradykinin (10 microg kg(-1) min(-1)) (+1 +/- 2 mm Hg, p < 0.05). In the control and MLA-pre-treated groups, (des-Arg9)-bradykinin had no effect.

CONCLUSION

MLA pre-treatment did not induce a hypotensive response to (des-Arg9)-bradykinin. We conclude that, in contrast to LPS, MLA does not induce B1-receptor synthesis, 24 h after its administration in the rabbit. Thus, the cardioprotective effects of MLA do not appear to be related to the kinin pathway.