title: Regional haemodynamic responses to adenosine receptor activation vary across time following lipopolysaccharide treatment in conscious rats.
abstract: OBJECTIVE
  Studies using adenosine receptor antagonists have shown that adenosine-mediated vasodilatations play an important role in the maintenance of regional perfusion during sepsis, but it is unclear whether vascular sensitivity to adenosine is affected. Here, we assessed regional haemodynamic responses to adenosine agonists and antagonists in normal and lipopolysaccharide (LPS)-treated rats to investigate a possible role for adenosine in the haemodynamic sequelae.
  
  
  METHODS
  Male Sprague-Dawley rats were chronically instrumented with pulsed Doppler flow probes to measure regional haemodynamic responses to adenosine-receptor agonists (adenosine, 2-choloro-N6-cyclopentyladenosine (CCPA)) and antagonists (8-phenyltheophylline (8-PT), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), at selected time points in control and LPS-treated rats.
  
  
  RESULTS
  The responses to 8-PT were consistent with endogenous adenosine causing bradycardia, and renal and hindquarters vasodilatation in control rats, whereas in LPS-treated rats, there was evidence for endogenous adenosine causing renal (at 1.5 h) and hindquarters (at 6 h) vasoconstriction. In control animals, exogenous adenosine caused hypotension, tachycardia and widespread vasodilatation, whereas in LPS-treated rats, the adenosine-induced renal (at 1.5 h) and hindquarters (at 6 h) vasodilatations were abolished. As enhanced A1 receptor-mediated vasoconstriction could explain the results in LPS-treated rats, vascular responsiveness to a selective A1-receptor agonist (CCPA) or antagonist (DPCPX) was assessed. There was no evidence for enhanced vasoconstrictor responsiveness to CCPA in LPS-treated rats, but DPCPX caused renal vasodilatation, consistent with endogenous adenosine mediating renal vasoconstriction under these conditions.
  
  
  CONCLUSIONS
  The results show changes in adenosine receptor-mediated cardiovascular effects in endotoxaemia that may have implications for the use of adenosine-based therapies in sepsis.
authors.affiliation: 1Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queens Medical Centre, University of Nottingham Medical School, Nottingham, UK.
authors.forename: L
authors.initials: L
authors.lastname: Jolly
authors.forename: J E
authors.initials: JE
authors.lastname: March
authors.forename: P A
authors.initials: PA
authors.lastname: Kemp
authors.forename: T
authors.initials: T
authors.lastname: Bennett
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D016503:Drug Delivery Systems; D018619:Echocardiography, Doppler, Pulsed; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D008070:Lipopolysaccharides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D018047:Receptors, Purinergic P1; D000241:Adenosine