Role of Nitric Oxide in Lipopolysaccharide-Induced Acute Lung Injury and Lipid Peroxidation in Rats / 대한마취과학회지

BACKGROUND: Nitric oxide (NO) may act as an oxygen radical scavenger or as an antioxidant, and inhibit neutrophil superoxide anion production. In contrast, NO combines with superoxide to form peroxynitrite, a very damaging material whose decomposition RESULTS in the generation of a hydroxyl radical. This study was designed to determine the role of NO in the development of acute lung injury and lipid peroxidation induced by lipopolysaccharide (LPS) in rats. METHODS: Male Sprague-Dawley rats (200 - 250 g) were given one of the following treatments; intraperitoneal normal saline 0.5 ml, intraperitoneal E. coli LPS (5 mg/kg) in 0.5 ml normal saline, 4 mg/kg L-N(6)-(1-iminoethyl)lysine (L-NIL) + LPS, or L-arginine (80 mg/kg) + LPS. Four hours after treatment, the rats were killed by an intraperitoneal pentobarbital injection (100 mg/kg) and plasma nitrate/nitrite concentration (Griess reagents) and lipid peroxide (LPO) concentration of the lung (Yagi's method) were measured (n = 8). In the other sets of experiments, myeloperoxidase activity of the lung (n = 5) and protein concentration of the bronchoalveolar lavage (BAL) fluid (BCA protein assay reagents, n = 4) were assayed. RESULTS: LPS treatment increased plasma nitrate/nitrite concentrations approximately 6 times (20.9 1.8nM, P < 0.01) compared with the control group (3.6 +/- 0.7nM), and L-NIL treatment prevented this increase. L-NIL plus LPS treatment resulted in greater increase of LPO concentrations of the lung compared with the control (P < 0.05). Myeloperoxidase activity and protein concentrations of BAL fluids were higher in LPS and L-NIL plus LPS treatment groups than the control group. CONCLUSIONS: These results suggest that inhibition of the increase of NO by selective inducible NO synthase inhibitor L-NIL may increase lipid peroxidation in septic rats.

Effects of L-NAME, Aminoguanidine and Hydroxocobalamin on Aortic Contractile Responses in Endotoxemic Rats during Halothane Administration / 대한마취과학회지

BACKGROUND: Recent studies demonstrated that volatile anesthetics suppress the NO-cGMP system in the vascular system. It has been known that the hemodynamic changes produced by volatile anesthetics in septic patients are mediated by upregulation of iNOS leading to excessive release of NO. The mechanisms underlying suppression of the NO-cGMP system by anesthetics are still controversial. It has been elucidated that nitric oxide synthase (NOS) plays a major role in the regulatory function in the L-arginine-NO system. So we examined the effects of NOS inhibitor (L-NAME, aminoguanidine) and NO scavenger (hydroxocobalamin) on vascular smooth muscle contractile function in lipopolysaccharide (LPS)-treated rat aorta during halothane administration. METHODS: Aortic ring preparations were obtained from LPS-treated (1.5 mg/kg, ip, for 18 h) rats. We evaluated the effects of hydroxocobalamin, L-NAME and aminoguanidine on contractile responses to phenylephrine during halothane (1 & 2 MAC) administration respectively. Statistical significances (P<0.05) were analyzed according to data characterictics by repeated measures ANOVA test and student's t-test. RESULTS: The contractile responses to phenylephrine in LPS-treated rats aorta were significantly (P<0.05) increased in the presence of hydroxocobalamin and L-NAME. During the halothane (1 and 2 MAC) administration, the contractile responses to phenylephrine in LPS-treated rats aorta were increased significantly (P<0.05) in the presence of hydroxocobalamin and L-NAME. CONCLUSIONS: From these results, it is suggested that hydroxocobalamin and L-NAME may be useful in the therapy of septic shock.

Effects of Inhalational Anesthetics on Contractile Responses and Nitric Oxide Synthase Activity in Endotoxemic Rats / 대한마취과학회지

BACKGROUND: Recent studies revealed that inhalational anesthetics (IA) attenuate NO production. But the hemodynamic changes produced by IA in septic syndrome patient are still sufficient to threaten patient, surgeon and anesthesiologist. So we examined which IA is proper to maintain vascular contractile force and evaluated the effects of NOS inhibitors on contractile force of septic rat aorta under IA. METHODS: Aortic ring preparation was obtained from LPS-treated (1.5 mg/kg, i.p. for 18h) rats. The development of sepsis was confirmed by iNOS activity and iNOS expression using RT-PCR. Contractile responses of aorta to phenylephrine admministation in the presence or absence of halothane, enflurane and isoflurane were evaluated. We also evaluated the effects of NOS inhibitors, one is NG-nitro-L-arginine methyl ester (L-NAME) and the other is aminoguanidine. Statistical significances (p<0.05) were analyzed according to data characteristics by unpaired t-test and paired t-test. RESULTS: The contractile responses to phenylephrine admministration were attenuated in LPS-treated rings. Isoflurane, even at the dose of 2 MAC, didn't affect the contractile response while both halothane and enflurane decreased the contractile response even at the dose of 1 MAC. The potentiation of contractile responses by NOS inhibitors were not affected during administeration of IA. CONCLUSIONS: From these results, it is suggested that isoflurane is the safest inhalational anesthetic and NOS inhibitors, especially L-NAME, may be very useful in the therapy of septic shock patients during general anesthesia.