The effects of Nω-nitro-L-arginine methyl ester(L-NAME)i.v.and nitric oxide(NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats...The effects of Nω-nitro-L-arginine methyl ester(L-NAME)i.v.and nitric oxide(NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats.Cocaine [4 mg/(kg. min) i.v.] produccd seizures then isoelectric electrocephalographic(isoEEG)activity as well as an initial increase in systolic blood pressure and heart rate,then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME[2 mg/(kg. min)i.v. ] for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8).Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. NO inhalation(80 ppm)did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.展开更多
Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the proba...Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the probable cardiovascular effect of NO in the dmPAG.Methods:Five groups(n=6 for each group)were used as follows:(1)control;(2)L-NAME(N^(G)-nitro-L-arginine methyl ester,a NO synthase inhibitor,90 nmol);(3)Larginine(L-Arg,a precursor for NO,60 nmol);(4)Sodium nitroprusside(SNP,a NO donor,27 nmol);and(5)L-Arg+L-NAME.The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery.Drugs were injected using a stereotaxic instrument.The changes(Δ)in systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)were calculated at different times and compared to the control group.Results:Microinjection of L-NAME significantly increased ΔSBP,ΔMAP,and ΔHR more than saline(from p<0.05 to p<0.001).L-Arg only significantly increased ΔHR(p<0.05).In the L-Arg+L-NAME group,the above parameters also significantly increased(from p<0.01 to p<0.05)but not as significantly as with L-NAME alone.Microinjection of SNP significantly decreased ΔSBP and ΔMAP more than in the control and L-NAME groups(from p<0.01 to p<0.001),but ΔHR did not change significantly.Conclusion:The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.展开更多
There is evidence that local anesthetic-induced seizures may be mediated by NMDA receptors which activate production of nitric oxide(NO).The objective of this study was to determine the effects,if any,of inhibition of...There is evidence that local anesthetic-induced seizures may be mediated by NMDA receptors which activate production of nitric oxide(NO).The objective of this study was to determine the effects,if any,of inhibition of NO synthesis on the responses of the central nervous and cardiovascular systems to bupivacaine.Sprague Dawley rats were assigned to two groups.The lightly anesthetized (0.5% halothane,70% N2O) and paralyzed (doxacurium) animals were given a NO synthase inhibitor[L-NAME,2 mg/(kg.min);n=6 ] of saline(n=5) i.v.for 30 min.Then bupivacaine was administered i.v. [2mg/(kg. min)]to both groups of animals until asystole.Arterial blood samples for bupivacaine concentration analysis (by HPLC)were taken during the stabilization period and during local anesthetic infusion. Student's t-test was used to determine significant differences(P< 0. 05) between groups. Average doses of bupivacaine that produced arrhythmias and asystole were remarkably lower in L-NAME vs. saline treated rats[arrhythmias (5.1±2.0)vs.(15.8±3. 8)mg/kg; asystole (15. 9±3. 2)vs.(27. 8±6.1)mg/kg; both P<0.05 ].The doses producing seizures and isoelectric EEG,and the duration of seizures did not differ significantly between the 2 treatment groups.However, EEG epileptiform activity was less intense (lower amplitude,shorter duration ietal activity) in the L-NAME treated animals.Arterial plasma concentrations of bupivacaine 5 min after the start of bupivacaine infusion were significantly higher in the L-NAME group.[(22, 3 ±2. 9)vs. (12. 8±1.5)mg/L, P<0. 05 ].These results suggest that NO synthase inhibition by L-NAME enhances the cardiac toxicity of bupivacaine probably by a pharmacokinetic action and reduces the central nervous system toxicity of bupivacaine probably by a pharmacodynamic action.展开更多
Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxid...Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxide synthase (NOS), mucosa structure and survival rate of intestinal gland were examined by using NADPH-diaphorase histochemistry, H-E staining, Feulgen’s reaction and intestinal gland counting techniques. Results: Compared with irradiated mice without (L--NAME ) treatment, the dilatation of intestinalcavity and blood vessels of mice treated with L-NAME were lessened, the survival rates of intestinal glandwere remarkably increased (P < 0. 01), the mucosal structure was obviously improved, and the amount ofNOS--positive structures or products were also reduced. Conclusion: Activation of NOS or increase of NOsynthesis might aggravate the acute pathological injuries of intestines of the irradiated mice, whereas administration of L-NAME has protective effect on the intestinal mucosa to certain extent.展开更多
The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the sm...The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the small intestine in fasting and red states arter intravenous infusionof N'-nitro-L-arginine methyl ester (L-NAME ), L-arginin., D-arglnine, sodium nitropusside(NaNP) and angiotensin 1 respectively. The results showed that intravenous inrusion or L-NAME,a NO synthase inhibitor, induced a fasting-like MMC motor pattern in fed rats. Infusion of NaNP, aNO donor, disrupted small intestinal MMC in fasting rats, inducing a postprandial-like motor pattern. Both fasting and postprandial, infusion of L-NAME shortened the duration or Phase I andphase Ⅱ,but didn't chang. the duration, frequency, amplitude and s,eed or Propogatiou of thephaSe, Ⅲ-argining, not D-arginine infused together with L-NAME, prevented the effect of LNAME infusion. Infusion of L-arginine, D-arginine or angioteusin Ⅰ alone didn't modify the smallintestinal motor pattern. It suggests that an inhibition of NO synthesis may be involved in the initiation of the MMC motor pattern during fasting, whereas an increase of NO output relates to the occurrence of the fed motor pattern展开更多
文摘The effects of Nω-nitro-L-arginine methyl ester(L-NAME)i.v.and nitric oxide(NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats.Cocaine [4 mg/(kg. min) i.v.] produccd seizures then isoelectric electrocephalographic(isoEEG)activity as well as an initial increase in systolic blood pressure and heart rate,then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME[2 mg/(kg. min)i.v. ] for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8).Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. NO inhalation(80 ppm)did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.
文摘Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the probable cardiovascular effect of NO in the dmPAG.Methods:Five groups(n=6 for each group)were used as follows:(1)control;(2)L-NAME(N^(G)-nitro-L-arginine methyl ester,a NO synthase inhibitor,90 nmol);(3)Larginine(L-Arg,a precursor for NO,60 nmol);(4)Sodium nitroprusside(SNP,a NO donor,27 nmol);and(5)L-Arg+L-NAME.The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery.Drugs were injected using a stereotaxic instrument.The changes(Δ)in systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)were calculated at different times and compared to the control group.Results:Microinjection of L-NAME significantly increased ΔSBP,ΔMAP,and ΔHR more than saline(from p<0.05 to p<0.001).L-Arg only significantly increased ΔHR(p<0.05).In the L-Arg+L-NAME group,the above parameters also significantly increased(from p<0.01 to p<0.05)but not as significantly as with L-NAME alone.Microinjection of SNP significantly decreased ΔSBP and ΔMAP more than in the control and L-NAME groups(from p<0.01 to p<0.001),but ΔHR did not change significantly.Conclusion:The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.
文摘There is evidence that local anesthetic-induced seizures may be mediated by NMDA receptors which activate production of nitric oxide(NO).The objective of this study was to determine the effects,if any,of inhibition of NO synthesis on the responses of the central nervous and cardiovascular systems to bupivacaine.Sprague Dawley rats were assigned to two groups.The lightly anesthetized (0.5% halothane,70% N2O) and paralyzed (doxacurium) animals were given a NO synthase inhibitor[L-NAME,2 mg/(kg.min);n=6 ] of saline(n=5) i.v.for 30 min.Then bupivacaine was administered i.v. [2mg/(kg. min)]to both groups of animals until asystole.Arterial blood samples for bupivacaine concentration analysis (by HPLC)were taken during the stabilization period and during local anesthetic infusion. Student's t-test was used to determine significant differences(P< 0. 05) between groups. Average doses of bupivacaine that produced arrhythmias and asystole were remarkably lower in L-NAME vs. saline treated rats[arrhythmias (5.1±2.0)vs.(15.8±3. 8)mg/kg; asystole (15. 9±3. 2)vs.(27. 8±6.1)mg/kg; both P<0.05 ].The doses producing seizures and isoelectric EEG,and the duration of seizures did not differ significantly between the 2 treatment groups.However, EEG epileptiform activity was less intense (lower amplitude,shorter duration ietal activity) in the L-NAME treated animals.Arterial plasma concentrations of bupivacaine 5 min after the start of bupivacaine infusion were significantly higher in the L-NAME group.[(22, 3 ±2. 9)vs. (12. 8±1.5)mg/L, P<0. 05 ].These results suggest that NO synthase inhibition by L-NAME enhances the cardiac toxicity of bupivacaine probably by a pharmacokinetic action and reduces the central nervous system toxicity of bupivacaine probably by a pharmacodynamic action.
文摘Objective The pathological significance of nitric oxide (NO) in the intestinal type radiation sickness. Methods: The intestinal type radiation sickness of BALB/c mice were induced byCo γ-radiation, andthe nitric oxide synthase (NOS), mucosa structure and survival rate of intestinal gland were examined by using NADPH-diaphorase histochemistry, H-E staining, Feulgen’s reaction and intestinal gland counting techniques. Results: Compared with irradiated mice without (L--NAME ) treatment, the dilatation of intestinalcavity and blood vessels of mice treated with L-NAME were lessened, the survival rates of intestinal glandwere remarkably increased (P < 0. 01), the mucosal structure was obviously improved, and the amount ofNOS--positive structures or products were also reduced. Conclusion: Activation of NOS or increase of NOsynthesis might aggravate the acute pathological injuries of intestines of the irradiated mice, whereas administration of L-NAME has protective effect on the intestinal mucosa to certain extent.
文摘The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the small intestine in fasting and red states arter intravenous infusionof N'-nitro-L-arginine methyl ester (L-NAME ), L-arginin., D-arglnine, sodium nitropusside(NaNP) and angiotensin 1 respectively. The results showed that intravenous inrusion or L-NAME,a NO synthase inhibitor, induced a fasting-like MMC motor pattern in fed rats. Infusion of NaNP, aNO donor, disrupted small intestinal MMC in fasting rats, inducing a postprandial-like motor pattern. Both fasting and postprandial, infusion of L-NAME shortened the duration or Phase I andphase Ⅱ,but didn't chang. the duration, frequency, amplitude and s,eed or Propogatiou of thephaSe, Ⅲ-argining, not D-arginine infused together with L-NAME, prevented the effect of LNAME infusion. Infusion of L-arginine, D-arginine or angioteusin Ⅰ alone didn't modify the smallintestinal motor pattern. It suggests that an inhibition of NO synthesis may be involved in the initiation of the MMC motor pattern during fasting, whereas an increase of NO output relates to the occurrence of the fed motor pattern
