title: Regional and temporal changes in cardiovascular responses to norepinephrine and vasopressin during continuous infusion of lipopolysaccharide in conscious rats.
abstract: BACKGROUND
  Reduced pressor responsiveness to norepinephrine (NE) in sepsis is well documented but the associated regional haemodynamic changes are less well characterized, and there are varying reports of changes in haemodynamic responses to arginine vasopressin (AVP). We compared changes in regional haemodynamic responsiveness to AVP and NE during a 24 h continuous infusion of lipopolysaccharide (LPS) in conscious rats.
  
  
  METHODS
  Conscious, male Sprague-Dawley rats were infused with saline (0.4 ml h(-1)) or LPS (150 micro g kg(-1) h(-1)). Renal, mesenteric, and hindquarter haemodynamic responses to 3 min infusions of AVP (0.25, 0.625, and 1.25 ng kg(-1) min(-1)) or NE (75, 250, and 750 ng kg(-1) min(-1)) were assessed 2, 6, and 24 h after the onset of LPS or saline.
  
  
  RESULTS
  Two and six hours after the onset of LPS, all haemodynamic effects of NE were markedly reduced, but by 24 h, there was some recovery in the vasoconstrictor actions of NE although the pressor and bradycardic effects were still depressed. Two hours after the onset of LPS, the cardiovascular effects of AVP were depressed but there was some recovery in vascular responsiveness at 6 h. By 24 h, only the mesenteric vasoconstrictor effect of AVP was consistently reduced.
  
  
  CONCLUSIONS
  During low dose LPS infusion, there are differential changes in haemodynamic responsiveness to AVP and NE, which show different temporal and regional profiles of recovery with time. Furthermore, reduced pressor responsiveness to NE is not necessarily accompanied by a reduced capacity of vessels for vasoconstriction.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: T
authors.initials: T
authors.lastname: Bennett
authors.forename: R P
authors.initials: RP
authors.lastname: Mahajan
authors.forename: J E
authors.initials: JE
authors.lastname: March
authors.forename: P A
authors.initials: PA
authors.lastname: Kemp
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009638:Norepinephrine