Propofol improves endothelial dysfunction and attenuates vascular superoxide production in septic rats

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 (O_2.-), in septic animals. Design: Prospective, multiexperimental, randomized, controlled studies. Setting: University research laboratory. Subjects: Male adult Sprague-Dawley rats weighing 350-400 g. Interventions: Cecal ligation and puncture (CLP), with and without propofol (25 mg/kg/hr) infusion, after sham or CLP (24 hrs postsurgery). Measurements and Main 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 O_2.- 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 O _2.- production in all rings, with significantly more increase in CLP vs. sham (p < .001). Propofol attenuated the excessive increase in O _2.- production of CLP rings. Conclusions: Propofol treatment attenuated the overproduction of NO and O_2.-, 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/O_2.- balance in sepsis.