title: Sympathetic Vasoconstrictor Responsiveness of the Leg Vasculature During Experimental Endotoxemia and Hypoxia in Humans.
abstract: OBJECTIVE
  Sympathetic vasoconstriction regulates peripheral circulation and controls blood pressure, but sepsis is associated with hypotension. We evaluated whether apparent loss of sympathetic vasoconstrictor responsiveness relates to distended smooth muscles or to endotoxemia and/or hypoxia.
  
  
  METHODS
  Prospective descriptive study.
  
  
  METHODS
  Hospital research laboratory.
  
  
  METHODS
  Ten healthy young men (age [mean ± SD], 31 ± 8 yr; body weight, 83 ± 10 kg) participated in the study.
  
  
  METHODS
  Leg blood flow and mean arterial pressure were determined, whereas leg vascular conductance was calculated during 1) adenosine infusion (vasodilator control), 2) hypoxia (FIO2 = 10%), 3) endotoxemia, and 4) endotoxemia + hypoxia. Leg sympathetic vasoconstrictor responsiveness (reduction in leg vascular conductance) was evaluated by femoral artery tyramine infusion.
  
  
  RESULTS
  Endotoxemia increased body temperature from 36.9 ± 0.4°C to 38.6 ± 0.5°C (p < 0.01) and plasma tumor necrosis factor-α from 6 pg/mL (3-8 pg/mL) to 391 pg/mL (128-2258 pg/mL) (p < 0.01; median [range]). Mean arterial pressure decreased similarly during endotoxemia (-11% ± 16%) and endotoxemia + hypoxia (-10% ± 15%; both p < 0.05). Leg blood flow and leg vascular conductance were not affected by endotoxemia, whereas both were elevated by adenosine infusion (leg blood flow, +94% ± 61%; leg vascular conductance, +97% ± 57%), hypoxia (leg blood flow: +93% ± 58%; leg vascular conductance, +100% ± 115%), and endotoxemia + hypoxia (leg blood flow, +67% ± 120%; leg vascular conductance, +65% ± 57%; p < 0.05). Endotoxemia lessened the tyramine-induced reduction in leg vascular conductance (-28% ± 13%) compared with the reduction during adenosine infusion (-47% ± 5%; p < 0.05). Also, endotoxemia + hypoxia (-17% ± 21%) attenuated the tyramine-induced reduction in leg vascular conductance compared with both adenosine infusion and hypoxia (-45% ± 13%; p < 0.05).
  
  
  CONCLUSIONS
  Both endotoxemia and combined hypoxia and endotoxemia blunted sympathetic vasoconstrictor responsiveness. Furthermore, tyramine normalized the doubled leg vascular conductance during administration of adenosine, suggesting that distension of vascular smooth muscles does not explain blunted sympathetic vasoconstrictor responsiveness during endotoxemia.
authors.affiliation: 1The Copenhagen Muscle Research Center, Copenhagen, Denmark. 2Department of Anesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Patrice
authors.initials: P
authors.lastname: Brassard
authors.forename: Morten
authors.initials: M
authors.lastname: Zaar
authors.forename: Pia
authors.initials: P
authors.lastname: Thaning
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Jaya B
authors.initials: JB
authors.lastname: Rosenmeier
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000503:physiopathology*; D005263:Femoral Artery / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007866:Leg / Q000098:blood supply*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000241:Adenosine; D009638:Norepinephrine; D014439:Tyramine