L-arginine administration ameliorates serum and pulmonary cytokine response after gut ischemia-reperfusion in immature rats

AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats. METHODS: Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor a (TNFα) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage. RESULTS: When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17±42.93 μmol/L) when compared with IR group (87.57±23.17 μmol/L, t=3.190, P= 0.008 <0.01). Serum MDA reduced significantly in IR+L-arg group (8.93±1.50 nmol/L) when compared with SHAM (23.78±7.81 nmol/L, t= 3.243, P= 0.007<0.01) and IR (25.54±9.32 nmol/L, t= 3.421, P= 0.006<0.01). ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81±7.84 pg/mL) than that in SHAM (35.52±10.82 pg/mL, t= 2,571, P= 0,03<0.05) and IR (50.83±22.05 pg/mL, t= 3.025, P= 0.009<0.01) groups. MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73±1.99 nmol/L) than in SHAM (16.62±2.28 nmol/L, t= 3.280, P = 0.007<0.01) and IR (21.90±4.82 nmol/L, t= 3.322, P= 0.007<0.01) groups. Serum and lung TNFα concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50±8.92, 33.20±16.59, and 22.50±6.09 in SHAM, IR, and IR+L-arg groups, respectively. CONCLUSION: Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group. L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO). METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissue malondialdehyde (MDA) content, and severity of hepatic I/R injury. RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs45.3μ10.1 μmol/L, P<0.01). Although serum NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P<0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18μg/L and 0.86±0.11 μmol/g, respectively, P<0.01). I/R induced significant injury to the liver both in M and F groups (P<0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P<0.05 and P<0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P<0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β-estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P<0.01). The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOS-derived NO.     

Insulin resistance is associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects

Type 2 diabetes is an insulin-resistant state characterized by hyperinsulinemia and accelerated atherosclerosis. In vitro and in vivo studies in rodents have suggested that nitric oxide generation plays an important role in glucose transport and insulin action. We determined nitric oxide synthase (NOS) activity in skeletal muscle of 10 type 2 diabetic (hemoglobin A(1C) = 6.8 +/- 0.1%) and 11 control subjects under basal conditions and during an 80 mU/m(2).min euglycemic insulin clamp performed with vastus lateralis muscle biopsies before and after 4 h of insulin. In diabetics, insulin-stimulated glucose disposal (Rd) was reduced by 50%, compared with controls (5.4 +/- 0.3 vs. 10.4 +/- 0.5 mg/kg.min, P < 0.01). Basal NOS activity was markedly reduced in the diabetic group (101 +/- 33 vs. 457 +/- 164 pmol/min.mg protein, P < 0.05). In response to insulin, NOS activity increased 2.5-fold in controls after 4 h (934 +/- 282 pmol/min.mg protein, P < 0.05 vs. basal), whereas insulin failed to stimulate NOS activity in diabetics (86 +/- 28 pmol/min.mg protein, P = NS from basal). Basal NOS protein content in muscle was similar in controls and diabetics and did not change following insulin. In controls, insulin-stimulated NOS activity correlated inversely with fasting plasma insulin concentration (r = -0.58, P = 0.05) and positively with Rd (r = 0.71, P = 0.03). In control and diabetic groups collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.52, P = 0.02). We conclude that basal and insulin-stimulated muscle NOS activity is impaired in well-controlled type 2 diabetic subjects, and the defect in insulin-stimulated NOS activity correlates closely with the severity of insulin resistance. These results suggest that impaired NOS activity may play an important role in the insulin resistance in type 2 diabetic individuals.     

Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats

AIM： To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS： A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group （n = 6）, transplant control group （n = 6）, and aminoguanidine （AG） treatment group （n = 18）. In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide （NO） level, blood sugar and amylase activity were detected. Nitric oxide synthase （NOS） test kit was used to detect the pancreas cNOS and inducible NOS （iNOS） activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS： As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG （80 mg/kg body weight） group showed the most significant difference in NO and amylase （NO： 66.0 ± 16.6 vs 192.3 ± 60.0, P 〈 0.01 and amylase： 1426 ± 177 vs 4477± 630, P 〈 0.01）. The expression and activity of tissue iNOS, and blood sugar in the AG （80 mg/kg body weight） group were much lower than those in the transplant control group （iNOS： 2.01 ± 0.23 vs 26.59 ±5.78, P 〈 0.01 and blood sugar： 14.2 ±0.9 vs 16.8 ± 1.1, P 〈 0.01）. CONCLUSION： Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.     

Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver

AIM： TO investigate the protective effects and possible mechanisms of Veratrum nigrum L. var. ussuriense Nakai alkaloids （VnA） on hepatic ischemia/reperfusion （I/R） injury in rats.
METHODS： Forty male Wistar rats were randomly divided into four experimental groups （n = 10 in each）： （A） Control group （the sham operation group）; （8） I/R group （pretreated with normal saline）; （C） Small-dose （10 μg/kg） VnA pretreatment group; （D） Large-dose （20 μg/kg） VnA pretreatment group. Hepatic ischemia/ reperfusion （Hepatic I/R） was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase （SOD） activity, myeloperoxidase （MPO） activity and nitric oxide （NO） content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 （ICAM-1） and E-selectin （ES） were detected by immunohistochemical examinations and Western blot analyses.
RESULTS： The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine aminotransferase （ALT： 74.53 ± 2.58 IU/L vs 1512.54 ± 200.76 IU/L, P 〈 0.01） and lactic dehydrogenase （LDH： 473.48 ± 52.17 IU/L vs 5821.53 ± 163.69 IU/L, P 〈 0.01）, as well as the levels of MPO （1.97 ± 0.11 U/g vs 2.57 ± 0.13 U/g, P 〈 0.01） and NO （69.37 ± 1.52 μmol/g protein vs 78.39 ± 2.28 μmol/g protein, P 〈 0.01） in the liver tissue, all of which were reduced by pretreatment with VnA, respectively （ALT： 1512.54 ± 200.76 IU/L vs 977.93 ± 89.62 IU/L, 909.81 ± 132.76 IU/L, P 〈 0.01, P 〈 0.01; LDH： 5821.53 ± 163.69 IU/L vs 3015.44 ± 253.01 IU/L, 2448.75 ± 169.4 IU/L, P 〈 0.01, P 〈 0.01; MPO： 2.57 ± 0.13 U/g vs 2.13 ± 0.13 U/g,     

一氧化氮及其合酶在哮喘发病机制中的作用

探讨一氧化氮及其合酶在哮喘发病机制中的作用。方法 采用哮喘豚鼠模型，将豚鼠分为４组；１．哮喘组，用１０％卵白蛋白腹腔注射１ｍｌ致敏，２周后用１％卵白蛋白超声雾化吸入致其哮喘发作．２；肾上腺皮质激素预防组；诱喘同哮喘组，在每次诱喘前腹腔滴注地塞米松０．５ｍｇ／ｋｇ。３．硝基精氨酸甲酯预防组；诱喘同哮喘组，每次诱喘产腹腔注射ＬＮＮＡ０．４ｍｇ／ｋｇ。４．正常对照组；用生理盐水代替诱喘剂。每组分别测定其     

肝细胞一氧化氮合酶的诱导及动力学研究

目的对内毒素和几种细胞因子诱导肝细胞一氧化氮合酶的协同效应及酶动力学参数进行研究.方法原位预灌流和段原酶循环灌流大鼠肝脏、分离肝实质细胞,观察内毒素、IFN-Y、IFN-α、TNFα、IL-lβ、IL-6及不同组合对肝细胞一氧化氮合酶活性、cGMP及NO2-+NO3的影响,分析酶动力学特征及皮质甾与酶诱导的量效关系.结果内毒素+IFN-v+TNFα+IL-lβ(IL-6)组合诱导酶表达效应最显著;酶参数分析显示Km、Vmax分别为108μmol/L和2632pmol@min1mg-1蛋白质,竞争性抑制剂L-NMMA、L-NNA作用的Ki分别为056μmolL及094μmol/L;诱导时间进程显示iNOS活性表达在9h达到峰值,但cGMP及NO2-NO3-的释放持续增加可维持至l8h;地塞米松和氢化可的松抑制肝细胞酶诱导的IC50分别为35×10-8mol/L和26×10-0mol/L.结论肝细胞诱导性一氧化氮合酶的表达依赖特异多细胞因子协同作用,这种可诱导性特征可能在内毒素血症和败血症休克发病机制中具有重要意义.     

Endothelin-1 and nitric oxide levels in patients with mitral annulus calcification

Mitral annulus calcification (MAC) is a chronic degenerative noninflammatory process. The goal of this study was to determine endothelin-1 (ET-1) and nitric oxide (NOx) levels in patients with MAC and compare them with those in normal subjects. The study group included 39 patients [26 females (66%), age, 63 +/- 8 years] with MAC and 20 [11 females (55%), age, 61 +/- 7 years] healthy subjects. The patients were divided into two subgroups, group A with severe MAC and group B with mild MAC, according to the severity of the MAC. Plasma ET-1 levels were higher and NOx levels were lower in patients than controls [(6.5 +/- 5.6 pg/mL vs 3.7 +/- 2.9 pg/mL for ET-1 and 35.0 +/- 10.6 micromol/L vs 42.3 +/- 9.9 micromol/L for NOx; P < 0.05 for both)]. In the subgroups, ET-1 levels were higher in group A than group B (8.65 +/- 6.84 pg/mL vs 4.74 +/- 3.45 pg/mL, P < 0.05) and the control group (8.65 +/- 6.84 pg/mL vs 3.70 +/- 2.88 pg/mL, P < 0.05). There was no difference between group B and the control group. Plasma NOx levels were significantly decreased in group A compared to controls (32.22 +/- 11.88 micromol/L vs 42.25 +/- 9.99 micromol/L, P < 0.05). However, no significant difference was observed between group B (37.38 +/- 9.06 micromol/L) and the other groups. Diabetes mellitus, coronary artery disease, and dyslipidemia were significantly associated with ET-1 levels. However, this association was not observed for NOx. In conclusion, patients with MAC have increased ET-1 and decreased NOx levels. This seems to be more prominent in patients with severe MAC.     

beta(2)-adrenoceptors activate nitric oxide synthase in human platelets

Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L-citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to 0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively (P<0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca(2+). In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2% respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through beta(2)ARs, as determined by coincubation with betaAR subtype-selective antagonists. We conclude that beta(2)ARs activate platelet NOS by increasing cAMP, and that this activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the L-arginine/NO system mediates the effects of beta(2)ARs on adhesion but not aggregation.     

Carvedilol action is dependent on endogenous production of nitric oxide

BACKGROUND: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). METHODS: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, iv). RESULTS: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 micromol/L to 32.2 +/- 2.5 micromol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 micromol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 micromol/L). CONCLUSIONS: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.