title: Propofol improves endothelial dysfunction and attenuates vascular superoxide production in septic rats.
abstract: OBJECTIVE
  To determine the effects of propofol on vascular functions, plasma and endothelium-derived nitric oxide (EDNO), vascular NO, and cyclic guanosine monophosphate (cGMP), as well as vascular production of superoxide anion (O2*-), in septic animals.
  
  
  METHODS
  Prospective, multiexperimental, randomized, controlled studies.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male adult Sprague-Dawley rats weighing 350-400 g.
  
  
  METHODS
  Cecal ligation and puncture (CLP), with and without propofol (25 mg/kg/hr) infusion, after sham or CLP (24 hrs postsurgery).
  
  
  RESULTS
  Plasma NOx, basal aortic NOx, and cGMP concentrations all increased, whereas acetylcholine-induced endothelium-dependent relaxation (EDR), contractile response, and EDNO all decreased in CLP vs. sham rats (p < .001). Acetylcholine stimulated aortic NOx and cGMP significantly in sham and CLP-propofol (p < .01) but not CLP rats. Thus, propofol ameliorated the CLP-induced increases in plasma NOx, basal aortic NOx, and cGMP. It restored the CLP-induced impairment of EDR, EDNO, and acetylcholine-stimulated aortic NOx and cGMP levels. More O2*- production (measured by lucigenin-enhanced chemiluminescence) was noted in carotid arteries from CLP vs. sham rats (p < .001). Nicotinamide adenine dinucleotide (NADH; 1 mM) stimulated O2*- production in all rings, with significantly more increase in CLP vs. sham (p < .001). Propofol attenuated the excessive increase in O2*- production of CLP rings.
  
  
  CONCLUSIONS
  Propofol treatment attenuated the overproduction of NO and O2*-, thus restoring the acetylcholine-responsive NO-cGMP pathway in CLP-induced sepsis. It also significantly improved the CLP-impaired EDR and EDNO in a parallel manner. These beneficial effects of propofol could be accounted for by improvement of the disturbed NO/O2*- balance in sepsis.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Ping-Wing
authors.initials: PW
authors.lastname: Lui
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Ying-Tung
authors.initials: YT
authors.lastname: Lau
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D006993:Hypnotics and Sedatives; D007773:Lactates; D013481:Superoxides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP; D015742:Propofol