title: Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.
abstract: N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion. Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host.
authors.affiliation: School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham NG7 2UH, UK. sheila.gardiner@nottingham.ac.uk
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: S R
authors.initials: SR
authors.lastname: Chhabra
authors.forename: C
authors.initials: C
authors.lastname: Harty
authors.forename: P
authors.initials: P
authors.lastname: Williams
authors.forename: D I
authors.initials: DI
authors.lastname: Pritchard
authors.forename: B W
authors.initials: BW
authors.lastname: Bycroft
authors.forename: T
authors.initials: T
authors.lastname: Bennett
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D006714:Homoserine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008643:Mesentery / Q000098:blood supply; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D008070:Lipopolysaccharides; C109860:N-(3-oxododecanoyl)homoserine lactone; D001262:Atenolol; D006714:Homoserine; D001285:Atropine; D015107:4-Butyrolactone