Effects of Nitric Oxide Synthase Inhibitor on Vascular Responses of Lidocaine and Bupivacaine in Endotoxemic Rats Aorta / 대한마취과학회지

BACKGROUND: Various local anesthetics have been shown to cause relaxation of isolated vascular rings contracted by phenylephrine. Recent studies reported that local anesthetics enhance nitric oxide (NO) production by human peripheral neutrophils. The author measured the effects of local anesthetics of nitrite production in LPS-treated rat aortic vascular smooth muscle cells and examined the effects of NW-nitro-L-arginine methyl ester (NAME) on vascular relaxant responses of lidocaine and bupivacaine in LPS-treated rat aortic rings. METHODS: Aortic ring preparations were obtained from LPS-treated (1.5 mg/kg, i. p. for 18hours) rat. Contractile responses of aorta to phenylephrine in dose-dependent administeration of lidocaine and bupivacaine (10(-6)M 10(-3)M) was examined. And also evaluated the effects of NAME (10(-6), 10(-5) and 10(-4)M) on relaxant responses of lidocaine and bupivacaine in LPS-treated rat aortic rings. From the cultured vascular smooth muscle cells, nitrite production of lidocaine and bupivacaine were measured by Griess reaction method. RESULTS: Lidocaine and bupivacaine enhanced the production of nitrite, the stable end product of nitric oxide, in cultured media of the vascular smooth muscle cells of the rat aorta but it didn't enhance significantly. NAME enhanced the contractile responses to lidocaine and bupivacaine in the LPS-treated rats significantly (p<0.05) but it didn't increase dose-dependently. CONCLUSION: These results show that lidocaine and bupivacaine increased NO production slightly in the LPS-treated rats and the vascular relaxant responses of local anesthetics were more enhanced because of NO production in LPS-treated rat.

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.

Effects of Hydroxocobalamin on Thiopental-Induced Contractile Responses of Septic Rat Thoracic Aorta / 대한마취과학회지

BACKGROUND: Endotoxins play important roles in the pathophysiologic alterations associated with sepsis so the authors examined the effects of hydroxocobalamin, NW-nitro-L-arginine-metyl ester (L-NAME) and aminoguanidine on thiopental-induced contractile responses of lipopolysaccharide (LPS)-treated and control rat aortic rings. METHODS: Aortic ring preparation was obtained from LPS-treated (1.5mg/kg, i.p. for 18h) rats. Cumulative doses of thiopental (10-4~3x10- 3M) were added to construct contraction response curves. Hydroxocobalamin (10-5M), L-NAME (10-6M) or aminoguanidine (10-6M) were added as NO scavenger or as NOS inhibitors. Contraction curves by cumulative doses of thiopental (10-4~3x10-3M) were remeasured after treatment of NO scavenger or NOS inhibitors. Statistical significances (p<00.05) were analyzed according to data characteristics by Student's t-test, paired t-test or ANOVA. RESULTS: The vascular responses of cumulative thiopental (10-4~3x10 3M) administration were dose- dependent contraction and LPS-treated rat was less contracted (p<00.05). There was significant increment on vascular contraction induced by thiopental after hydroxocobalamin pretreatment in LPS-treated rat (p<0.05), in spite of L-NAME, aminoguanidine pretreatment was failed to increase contractile forces in control and LPS-treated rats. CONCLUSIONS: From these results, viewed from maintenance of vasomotor tone in septic state, it is suggested that hydroxocobalamin may be candidate for vasopressor during usual induction of general anesthesia.

Effects of Volatile Anesthetics on Aortic Contractile Responses in Endotoxemic Rats / 대한마취과학회지

BACKGROUND: Endotoxins play important roles in the pathophysiologic alterations associated with sepsis so we examined the effects of volatile anesthetics on vascular smooth muscle contractile function in LPS-treated rat aorta. METHODS: Fifty male Sprague-Dawley rats(250~300 gm) were made septic by intraperitoneal injection of lipopolysaccharide(1.5 mg/kg). Cumulative doses of phenylephrine and norepinephrine(10 -8~10 -5M) were added to construct a contraction response curve. Two percent of volatile anesthetics, IBMX (3-isobutyl-1-methylxanthine, phosphodiesterase inhibitor) or L-NAME(Ng-nitro-L-arginine-methylester, Nitric oxide synthase inhibitor) was added and those contractile responses were observed respectively. We also measured nitric oxide synthase (NOS) activity of liver, lung and adrenal gland after 18 hours in the LPS-treated rats. Individual values between the control rats and LPS-treated rats were compared by unpaired t-test. A p-value less than 0.05 was considered statistically significant. RESULTS: Contractile response of 2% halothane to norepinephrine was significantly decreased both in the control rats and LPS-treated rats. The NOS inhibitor enhanced the contractile responses to phenylephrine and norephinephrine in the vessels from LPS-treated rats more significantly than those of control rats. CONCLUSIONS: These results suggest that LPS-treatment impairs vasopressor-induced contractility and doesn't alter the contractile responses during administration of volatile anesthetics.