title: Uncoupling of coronary microvascular beta 2-adrenoceptors by Escherichia coli endotoxemia.
abstract: BACKGROUND
  Cardiovascular responses to the adrenergic stimulation are depressed in clinical and experimental endotoxemia. However, the effect of Escherichia coli endotoxemia on coronary microvascular beta-adrenergic function remains to be determined. The purpose of the present study was to test the hypothesis that endotoxemia impairs the beta-adrenoceptor- and adenosine 3'5'-cyclic monophosphate-mediated relaxation in the porcine coronary microcirculation.
  
  
  METHODS
  Coronary arterioles (80 to 170 microns internal diameter) were isolated from pigs 3 hours after intravenous administration of E. coli endotoxin (150 micrograms/kg, over 1 hour, n = 8) or Ringer's lactate (control, n = 8). Arterioles were studied in vitro in a pressurized, partially contracted, no-flow state by videomicroscopy.
  
  
  RESULTS
  Precontracted (30% to 50% of baseline diameter with acetylcholine) control coronary arterioles dilated in response to either the nonselective beta-adrenoceptor agonist, isoproterenol, the Gs-protein activator, sodium fluoride, or the adenylate cyclase activator, forskolin. After 3 hours of endotoxemia, the relaxation responses to isoproterenol and sodium fluoride were significantly reduced, but the relaxation response to forskolin was preserved. The beta 2-adrenoceptor blocker, ICI-118, 551, markedly reduced the relaxation of control microvessels induced by isoproterenol, whereas the beta 1-adrenoceptor blocker, atenolol, caused only a slight reduction in isoproterenol-induced relaxation.
  
  
  CONCLUSIONS
  beta 2-Adrenoceptors appear to predominate over beta 1-adrenoceptors in the coronary microcirculation. E. coli endotoxemia impairs beta 2-adrenoceptor-mediated relaxation in the porcine coronary microcirculation, apparently because of changes proximal to adenylate cyclase in the signal transduction pathway.
authors.affiliation: Department of Surgery, Beth Israel Hospital, Boston, MA 02215.
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: T J
authors.initials: TJ
authors.lastname: VanderMeer
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004926:Escherichia coli / Q000472:pathogenicity*; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000502:physiology; D013552:Swine
chemical_list: D008070:Lipopolysaccharides; D018343:Receptors, Adrenergic, beta-2; D005576:Colforsin; D007545:Isoproterenol