AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HO...AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HOCl on nuclear nucleoside triphosphatase of hepatocytes and the ability of taurine to prevent this effect were investigated.METHODS:Isolated hepatic nuclei from rat liver were exposed to HOCl with or without taurine. The NTPase activity on nuclear envelope was assayed using ATP and GTP as substrates, respectively.RESULTS:The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect NTPase.HOCI at 10^-9-5×10^-6 mol/L reduced nuclear NTPase activities in a concentration dependent manner (ATP and GTP as substrates) (P<0.01). HOCl at 10^-6mol/L reduced the NTPase activity by 65% (ATP as substrate) and 76% (GTP assubstrate). Taurine (10^-7 to 10^-4mol/L) was tested forprotection against HOCl at 10^-6mol/L and the nuclei treated with 5×10^-4mol/L taurine exhibited only 20% and 12% reduction in NTPase activities compared to untreated controls. A second study was performed comparing taurine to glutathione (GSH). GSH and HOCl at 10^-6mol/L exhibited 46% and 67.4% reduction in NTPase activities compared with control. GSH (10^-4mol/L) which was incubated with the nuclei and HOCI still exhibited 44.2% and 44.8% reduction in NTPase activities of untreated control. Taurine with HOCl only exhibited 15.2% and 17.1% reduction in NTPase activities, which provided more powerful protection against HOCI than GSH. The third experiment was undertaken to evaluate the specificity of taurine against HOCl. Incubation of rat hepatic nuclei with Fe^3+/H2O2 (1mmol/L vs 5μmol/L) resulted in a decrease in nuclear NTPase activities (P<0.01).When hepatic nuclei were incubated with Tau (10^-4mol/L) and Fe^3+/H2O2 (1mmol/L vs 5μmol/L), nuclear NTPase activities were only slightly increased as compared with that of incubation with Fe^3+/H2O2 alone. However, GSH failed to alter the NTPase activities induced by Fe^3+/H2O2.CONCLUSION:The present findings indicate that HOCl can act as an inhibitor of nuclear NTPase. Taurine can antagonistically reduce the toxicity of HOCI to NTPase.展开更多
To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced...To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]- ET1 binding. Marker enzyme activities, protein yield, and dry- to- wet weight ratio of cardiac membranes were measured. Results. Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]- ET1 binding study showed that during early stage of sepsis, the Bmax of ET1 receptors was increased by 30％ in sarcolemma but decreased by 19％ in light vesicles, while during late stage of sepsis, the Bmax was decreased by 24％ in sarcolemma but increased by 38％ in light vesicles.The total binding of sarcolemma and light vesicles was increased by 25％ during early stage of sepsis but decreased by 17％ during late stage of sepsis. Conclusions. These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.展开更多
The present study was designed to make certain whether there exists adrenomedullin (ADM) in the rat central nervous system and evaluated the hemodynamic actions of intracerebroventricular administration (ICVA) of hum...The present study was designed to make certain whether there exists adrenomedullin (ADM) in the rat central nervous system and evaluated the hemodynamic actions of intracerebroventricular administration (ICVA) of human ADM[13-52]. By immunohistochemistry (ABC method),We found that there was a discrete localization of ADM-positive immunoreactivity in the rat central system including cerebral cortex,paraventricular tissues, hypothalamus, cerebella cortex, mesencephalon and medulla oblongata. By reverse transcription-polymerase chain reaction(RT-PCR) analysis, rat ADM mRNA was found to be expressed in rat brain. These above results of immunohistochemistry and RT-PCR suggest that ADM exists in the rat brain. We also found that centrally administered ADM[13-52]in a dose of 0.4 to 3. 2 nmol/kg provoked marked, prolonged and dosedependent increases in mean arterial blood pressure (MABP) and heart rate (HR). To clarify the mechanisms of the hemodynamic changes induced by centrally administered ADM [13-52]. the effect of centrally administered ADM [13-52] on renal sympathetic nerve activity (RSNA) was studied. The result showed that centrally administered ADM [13-52] ( 1. 6 nmol/kg) provoked a marked increase in RSNA .therefore .the increases in MABP and HR induced by centrally administered ADM [13-52]might be due to the stimulation of central sympathetic mechanism. In addtion,we also compared the relationship of activity and structure among the different fragments of ADM. In conclusion, ADMexists in the rat brain, and it may play an important role in the central control of cardiovascular system.展开更多
Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6...Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .展开更多
In present study,we examined the effects of N-nitro-L-arginine（LNNA）,an inhibitor of nitric oxide synthase（NOS）,and/or methylene blue（MB）,a blocker of guanylate cyclase on the vasodilator response of isolated ra...In present study,we examined the effects of N-nitro-L-arginine（LNNA）,an inhibitor of nitric oxide synthase（NOS）,and/or methylene blue（MB）,a blocker of guanylate cyclase on the vasodilator response of isolated rat arteries including aorta and mesenteric artery to calcitonin展开更多
基金Supported by the Major State Basic Research Development Program of People's Republic of China,No.G2000056905 and the National Natural Science Foundation of China,No.30070308
文摘AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HOCl on nuclear nucleoside triphosphatase of hepatocytes and the ability of taurine to prevent this effect were investigated.METHODS:Isolated hepatic nuclei from rat liver were exposed to HOCl with or without taurine. The NTPase activity on nuclear envelope was assayed using ATP and GTP as substrates, respectively.RESULTS:The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect NTPase.HOCI at 10^-9-5×10^-6 mol/L reduced nuclear NTPase activities in a concentration dependent manner (ATP and GTP as substrates) (P<0.01). HOCl at 10^-6mol/L reduced the NTPase activity by 65% (ATP as substrate) and 76% (GTP assubstrate). Taurine (10^-7 to 10^-4mol/L) was tested forprotection against HOCl at 10^-6mol/L and the nuclei treated with 5×10^-4mol/L taurine exhibited only 20% and 12% reduction in NTPase activities compared to untreated controls. A second study was performed comparing taurine to glutathione (GSH). GSH and HOCl at 10^-6mol/L exhibited 46% and 67.4% reduction in NTPase activities compared with control. GSH (10^-4mol/L) which was incubated with the nuclei and HOCI still exhibited 44.2% and 44.8% reduction in NTPase activities of untreated control. Taurine with HOCl only exhibited 15.2% and 17.1% reduction in NTPase activities, which provided more powerful protection against HOCI than GSH. The third experiment was undertaken to evaluate the specificity of taurine against HOCl. Incubation of rat hepatic nuclei with Fe^3+/H2O2 (1mmol/L vs 5μmol/L) resulted in a decrease in nuclear NTPase activities (P<0.01).When hepatic nuclei were incubated with Tau (10^-4mol/L) and Fe^3+/H2O2 (1mmol/L vs 5μmol/L), nuclear NTPase activities were only slightly increased as compared with that of incubation with Fe^3+/H2O2 alone. However, GSH failed to alter the NTPase activities induced by Fe^3+/H2O2.CONCLUSION:The present findings indicate that HOCl can act as an inhibitor of nuclear NTPase. Taurine can antagonistically reduce the toxicity of HOCI to NTPase.
基金This study was supported by the National Nature Scientific Fund (No.39730220).
文摘To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]- ET1 binding. Marker enzyme activities, protein yield, and dry- to- wet weight ratio of cardiac membranes were measured. Results. Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]- ET1 binding study showed that during early stage of sepsis, the Bmax of ET1 receptors was increased by 30％ in sarcolemma but decreased by 19％ in light vesicles, while during late stage of sepsis, the Bmax was decreased by 24％ in sarcolemma but increased by 38％ in light vesicles.The total binding of sarcolemma and light vesicles was increased by 25％ during early stage of sepsis but decreased by 17％ during late stage of sepsis. Conclusions. These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.
文摘The present study was designed to make certain whether there exists adrenomedullin (ADM) in the rat central nervous system and evaluated the hemodynamic actions of intracerebroventricular administration (ICVA) of human ADM[13-52]. By immunohistochemistry (ABC method),We found that there was a discrete localization of ADM-positive immunoreactivity in the rat central system including cerebral cortex,paraventricular tissues, hypothalamus, cerebella cortex, mesencephalon and medulla oblongata. By reverse transcription-polymerase chain reaction(RT-PCR) analysis, rat ADM mRNA was found to be expressed in rat brain. These above results of immunohistochemistry and RT-PCR suggest that ADM exists in the rat brain. We also found that centrally administered ADM[13-52]in a dose of 0.4 to 3. 2 nmol/kg provoked marked, prolonged and dosedependent increases in mean arterial blood pressure (MABP) and heart rate (HR). To clarify the mechanisms of the hemodynamic changes induced by centrally administered ADM [13-52]. the effect of centrally administered ADM [13-52] on renal sympathetic nerve activity (RSNA) was studied. The result showed that centrally administered ADM [13-52] ( 1. 6 nmol/kg) provoked a marked increase in RSNA .therefore .the increases in MABP and HR induced by centrally administered ADM [13-52]might be due to the stimulation of central sympathetic mechanism. In addtion,we also compared the relationship of activity and structure among the different fragments of ADM. In conclusion, ADMexists in the rat brain, and it may play an important role in the central control of cardiovascular system.
文摘Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .
文摘In present study,we examined the effects of N-nitro-L-arginine（LNNA）,an inhibitor of nitric oxide synthase（NOS）,and/or methylene blue（MB）,a blocker of guanylate cyclase on the vasodilator response of isolated rat arteries including aorta and mesenteric artery to calcitonin
