Propofol-induced vascular permeability change is related to the nitric oxide signaling pathway and occludin phosphorylation.
The present study was undertaken to elucidate the mechanism of intra-arterial propofol-induced vascular permeability change resulting in tissue edema. The mechanism of propofol-induced hyperpermeability was examined in a rat femoral artery injection model. Vascular permeability was determined by measuring the Evans blue content of the dorsal skin of the infused limb at 15, 30, 45 and 60 min after propofol injection. The total content of the tight junction proteins occludin, ZO-1 and claudin-5 under experimental conditions was also determined by western blotting. Intra-arterial injection with propofol resulted in a marked dose-dependent increase in vascular permeability of the rat hindpaw. Pretreatment with 10 mg/kg of N-nitro-L: -arginine methyl ester (L: -NAME) but not aminoguanidine significantly inhibited the change in vascular permeability after challenge with propofol. Pretreatment with L: -arginine and nitroprusside increased the propofol-induced permeability change. Intra-arterial injection of propofol significantly increased occludin phosphorylation after 15 min, which was consistent with the time profile of the vascular permeability change. L: -NAME partially reversed the change in occludin phosphorylation, whereas aminoguanidine had no effect compared with that in the controls. Our observations indicate that nitric oxide (NO) is an important mediator in the induction of vascular permeability induced by propofol. Occludin phosphorylation is a determining factor in the vascular permeability change induced by propofol. NO synthase (NOS) inhibitors might be useful in the treatment of accidental intra-arterial injection of propofol, in the reduction of any adverse effects.
Chen
Yi-Shen
YS
Department of Anesthesiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, 123 Ta-Pei Rd, Niao-Sung Hsian, Kaohsiung, 833, Taiwan, ROC.
Chen
Kuan-Hung
KH
Liu
Chien-Cheug
CC
Lee
Chien-Te
CT
Yang
Chien-Hui
CH
Chuang
Kuan-Chih
KC
Lin
Chung-Ren
CR
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue / Q000032:analysis / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012867:Skin / Q000098:blood supply; D019108:Tight Junctions / Q000737:chemistry; D062826:Zonula Occludens-1 Protein
D004791:Enzyme Inhibitors; D006146:Guanidines; D006993:Hypnotics and Sedatives; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D009599:Nitroprusside; D009569:Nitric Oxide; D005070:Evans Blue; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D015742:Propofol