Induction of beta 1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide.
The intravenous injection of 10 microgram of a lipopolysaccharide extracted from E. Coli to rabbits leads to the appearance of a hypotensive effect for des-Arg9-BK and increases significantly the vasodilator effect of this peptide in isolated hearts and its contractile effects in strips of large arteries and veins. LPS elicits these responses when administered 5 or 20 h before anesthesia; the hypotensive response of animals receiving LPS just before anaesthesia is similar to that of untreated rabbits. All actions of des-Arg9-BK in vivo, in isolated hearts and in isolated tissues are blocked by des-Arg10,[Leu9]-kallidin (KD), a specific inhibitor of kinins B1-receptor. These data are taken as evidence of the appearance of B1-response to kinins in the few hours following LPS injection. The response of the animals, perfused organs and isolated tissues to other agonists, such as substance P or [Tyr(Me)8]-BK (an activator of B2-receptors for kinins) are not affected by the treatment with LPS nor are they modified by the antagonist des-Arg10,[Leu9]-KD. The present data, together with previous studies on the sensitization mechanism of B1-receptor containing preparations, suggest that LPS induces the formation of B1-receptors in the rabbit, within a few hours. The activation of B1-receptors by des-Arg9-BK produces hypotension, coronary vasodilation and stimulation of large arteries and veins isolated and suspended in vitro. Some large arteries and veins (e.g. the aorta and the anterior mesenteric vein) as well as some peripheral vascular beds (e.g. the coronary vessels) have the ability of generating B1-receptors, while other organs (e.g. the external jugular vein) have not or very little. The reason for this phenomenon as well as the intimate mechanism by which LPS induces the formation of B1-receptors remain to be elucidated.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D007705:Kinins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface / Q000187:drug effects*
D007705:Kinins; D008070:Lipopolysaccharides; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin