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Korean J Pediatr 1995 July;38(7) :922-935.
Studies on Mechanism of Vascular Hyporeactivity of Mesenteric Artery from Septic Rats
Man Chul Ha (Ha MC)1, Hee Ju Park (Park HJ)1, Ki Whan Hong (Hong KW)2
1Department of Pediatrics, College of Medicine, Pusan National University, Pusan, Korea
2Department of Pharmacology, College of Medicine, Pusan National University, Pusan, Korea
Copyright © 1995 by The Korean Pediatric Society
Purpose : Septic shock due to gram negative bacterial infection is characterized by vasodil-ation, hypotension, and myocardial depression due to the effect of lipopolysaccharide (LPS). In spite of extensive studies, the mechanisms for the vascular effects of endotoxemia are not clear. Recently, it has been proposed that nitric oxide (NO) synthesized from L-arginine by nitric oxide synthase contributes to the hypotension induced by lipopolysaccharide in the rat. Methods : In this study, it was purposed to investigate the mechanism of alteration in vascular responses in septic shock induced by the procedure of cecal ligation and puncture (CLAP), and the result was compared with those in the rats treated with E.Coli endotoxin, LPS. Results : 1) At 16 hour post-CLAP, all animals showed a positive blood culture for E.Coli. 2) The contractile responses of isolated mesenteric arterial strips from LPS-treated and CLAP rats to KCI (60 mM), phenylephrine and U44069 were significantly decreased in compari-son to control group. 3) Relaxant effects of acetylcholine on the precontraction by U44069 did not differ between control, LPS-treated and CLAP rats. 4) When inhibitory effects of L-arginine analogues on the acetylcholine relaxation were compared, NW-nitro-L-arginine (L-NNA) was more potent than NW-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) was without effect. These potency orders were similarly identified not only in control but also in LPS-treated and CLAP rats. 5) Acetylcholine-induced relaxation was characteristically induced in the mesenteric artery denuded of endothelium from LPS-treated and CLAP rats. 6) Acetylcholine-relaxation of the KCI (60 mM)-induced contraction was more prominent with lower ED50 value (P <0.01) in CLAP rats than in control rats. Conclusion : Based on these results, it is summerized that L-NNA-sensitive nitric oxide synthase activity is higher in the vascular beds from CLAP rat than that from control rats.
Keywords: Septic shock | Lipopolysaccharide | Nitric oxide | Endothelium-derived relaxing factor
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