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


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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.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 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.

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