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.


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.


CONCLUSIONS
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.
Mazenot
C
C
PCEBM, UFR de Pharmacie, Université Grenoble I, La Tronche, France.
Ribuot
C
C
Demenge
P
P
Godin-Ribuot
D
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D008050:Lipid A; D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; C048436:monophosphoryl lipid A; D001920:Bradykinin