The protection of the hepatic ischemic preconditioning is concerned with the NO/ET-1 system

AIM: To study the relationship between the disturbance of nitric oxide/endothelin-1(NO/ET-1) and hepatic ischemia/reperfusion(I/R) injury as well as the regulation of NO/ET-1 system by hepatic ischemic preconditioning(IPC). METHODS: The changes of NO/ET-1 system and their relationship with hepatic I/R injury were compared between I/R group and IPC+I/R group in a rat hepatic I/R model. Two hours after reperfusion, the liver tissues were detected by RT-PCR to see whether there was inducible nitric oxide synthase (iNOS) mRNA expression. RESULTS:In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to a significant reduction of NO₂^-/NO₃^- (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and of MDA in liver tissue were increased but ATP in liver tissue was reduced, the hepatic damage was deteriorated. The protection of the hepatic IPC was concerned with the elevation of the ratio of NO/ET-1 caused by the elevation of NO₂^-/NO₃^-, and reduction of ET-1 as well. There was no iNOS mRNA detected in the liver tissues.CONCLUSION: Hepatic I/R injury is related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be conducted by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this situation.     

Changes in endothelin-1 and atrial natriuretic factor and the effect of atrial natriuretic factor on the change of endothelin-1 in asthmatic guinea pigs

AIM: To investigate the possible role of endothelin(ET-1) in asthma pathogenesis and the effect of atrial natriuretic factor (ANF) on changes of ET-1. METHODS: Measuring the contents of endothelin-1(ET-1),atrial natriuretic factor(ANF),cGMP in plasma and bronchoalveolar lavage fluid (BALF) of guinea pigs. RESULTS: The contents of ET-1, ANF and cGMP in asthma group were higher than that of the control group; There was a significant negative correlation between ET-1 and ANF( r=-0.638,P <0.05) in plasma of the asthma group, and a significantly negative correlation between ET-1 and ANF( r=-0.921,P <0.01) in BALF of the asthma group. There was a significantly positive correlation between ANF and cGMP( r=0.848,P <0.01) in plasma of the asthma group,and a significantly positive correlation between ANF and cGMP ( r=0.831,P <0.01) in BALF of the asthma group. The levels ET-1 in the asthma+rat ANF(rANF) group were lower than those in the asthma group,and the levels of cGMP in the asthma+rat ANF(rANF) group were higher than those in the asthma group after ceasing to infuse rANF for guinea pigs for 30 minutes.CONCLUSION: ET-1 might play an important role in the pathogenesis of asthma.ANF might inhibit production of ET-1.     

Effect of lipopolysaccharide on viability and secretion function of human umbilical vein endothelial cells

AIM: To observe the direct effect of lipopolysaccharide (LPS) on secretion of endothelin-1 (ET-1) and nitric oxide by human umbilical vein endothelial cell and cell viability of the secretor. METHODS: The third passage of human umbilical vein endothelial cells were incubated with different concentrations of LPS (1 g/L, 100 mg/L, 10 mg/L, 1 mg/L, 100 μg/L, 10 μg/L, 1 μg/L) for 6 hours, and the culture supernatants were collected. The concentrations of ET-1 were determined by radioimmunoassay, the concentrations of nitric oxide were determined using Greiss's method. The viabilities of cells were measured by MTT method. RESULTS: The concentration of ET-1 (pg/L) of normal control group was 251.64±10.90. The concentrations of ET-1 (pg/L) of LPS treated groups were 220.85±19.14, 278.67±15.45, 306.40±11.60, 312.87±33.50, 324.38±17.02, 291.49±14.30, 282.11±13.38, respectively (each group compared with normal control group, P<0.05 or P<0.01). The concentration of NO_x (μmol/L) of normal control group was 629.46±13.36. The concentrations of NO_x (μmol/L) of LPS treated groups were 732.58±23.21, 669.87±9.32, 661.24±16.80, 650.33±13.24, 606.59±12.94, 626.75±9.83, 627.61±5.61, respectively (each group compared with normal control group, P<0.05 or P<0.01). The viabilities of endothelial cells of LPS treated groups were 74%, 81%, 86%, 88%,91%, 93%, 93%, respectively. CONCLUSION: LPS of lower concentrations had no significantly lethal effect on human umbilical vein endothelial cells, but enhanced secretion of ET-1 and inhibited NO production. LPS in higher concentrations showed significant lethal effect on human umbilical vein endothelial cells, inhibited secretion of ET-1 and enhanced NO production.     

Effect of L-Arg on plasma content of endothelin and expression of c-fos mRNA in the left ventricle of rats with renovascular hypertensive hypertrophy

AIM:To study the effect of L-Arg on plasma content of endothelin (ET) and the expression of proto-oncogene c-fos mRNA in the left ventricle of rats with renovascular hypertensive hypertrophy. METHODS: The level of c-fos mRNA were measured by in situ hybridization. The ET in plasma were measured by radioimmunoassay. RESULTS:After eight weeks of treatment with L-Arg, the expression of c-fos decreased markedly (P＜0.01). The ET content in plasma also decreased significantly by L-Arg(P＜0.01).CONCLUSION: Plasma ET content and the expression of c-fos in the left ventricle of rats with renovascular hypertensive hypertrophy could be decreased by L-Arg administration.     

Impact of hydrogen sulfide donor on endothelin-1 and connective tissue growth factor expression in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To explore the possible impact of hydrogen sulfide (H2S) donor-sodium hydrosulfide (NaHS) on endothelin-1 (ET-1) and connective tissue growth factor (CTGF) expressions in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty-two male SD rats were randomly divided into 4 groups: shunt group, shunt+NaHS group, sham group and sham+NaHS group. Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 11 weeks of experiment, rat systolic pulmonary artery pressure (SPAP), lung tissue H2S, plasma ET-1 concentration and lung tissue ET-1mRNA expression, as well as pulmonary artery CTGF protein expression were detected.RESULTS: After 11 weeks of experiment, SPAP, lung tissue ET-1mRNA, plasma ET-1 as well as pulmonary artery CTGF expressions were increased markedly, respectively, whereas H2S in lung tissue decreased significantly in rats of shunt group as compared with that in sham group (all P<0.05). After administration of NaHS for 11 weeks, H2S in lung tissue increased significantly, whereas SPAP, plasma ET-1 and lung tissue ET-1 mRNA expression as well as pulmonary artery CTGF protein expression decreased significantly, respectively, in rats of shunt+NaHS group as compared with that in shunt group (all P<0.05).CONCLUSION: NaHS might be involved in the development of pulmonary hypertension induced by high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expressions in lung tissues of rats.     

Effects of taurine-magnesium complex on vascular endothelium and hemorheology in rats in vivo

AIM: To study the protective effects of taurine-magnesium complex (TMC) on endothelium and hemorheology in rats. METHODS: A model of the endothelial damage was made by means of giving rats an injection of adrenaline and making them swim in ice-cold water, then number of circulating endothelial cells (CEC) in whole blood, plasma ET-1 and NO₂^-/NO₃^- content, NOS activity and rheology were determined, respectively. The protective effects of TMC were also observed. RESULTS: An increase in the number of CEC accompanied by abnormal whole blood viscosity, and endothelium-derived ET-1 were observed in model rats. Both the NO₂^-/NO₃^- content and NOS activity were declined significantly in model rats. TMC reduced the number of CEC, resumed NO₂^-/NO₃^- content and NOS activity, and improved the whole blood viscosity in a dose-dependent manner in model rats. CONCLUSION: Ice-cold water bath with adrenaline causes an acute damage of vascular endothelium and abnoramal rheology. TMC protects against the injury of vascular endothelium and improves the hemorheology.     

The changes of intrarenal endothelin system in the course of congestive heart failure induced by rapid right ventricular pacing in dogs

AIM: To investigate the changes of intrarenal endothelin system in the course of congestive heart failure. METHODS: A canine congestive heart failure model induced by rapid right ventricular pacing was used in the present study. Twenty-one mongrel dogs divided randomly into 3 groups: control, congestive heart failure 2 weeks (CHF2) and congestive heart failure 4 weeks (CHF4). The severity of heart failure was evaluated by means of hemodynamic measurement. The concentration of plasma endothelin was detected via RIA, and the expression of endothelin was detected by RT-PCR. RESULTS: The concentration of plasma endothelin in both of CHF2 and CHF4 elevated significantly. In CHF2, the expression of endothelin receptor B(ETB) in renal medulla increased significantly. And in CHF4, the expression of preproendothelin, endothelin receptor A (ETA) and ETB increased both in renal cortex and medulla. Furthermore, in cortex, the expression of ETA increased more significantly than ETB, while in medulla, ETB expressed much more than ETA. CONCLUSION: The changes of renal endothelin system expression plays a role in the regulation of water and electrolyte balance during the progress of congestive heart failure.     

Insulin influences the vasoconstriction caused by endothelin-1 in the hyperglycemic rat

AIM: To investigate the effects of insulin on aortic constriction caused by endothelin-1(ET-1) in normal and hyperglycemic rats. METHODS: Hyperglycemic rat models were prepared. Two aortic rings were immersed in the Krebs-Hensleit fluid with and without insulin (40 mIU/L) and the responses of rings to 10^-9 mol/L ET-1 were observed. RESULTS:ET-1 induced more obvious aortic ring constriction in normal rats than those in hyperglycemic rats ( P< 0.01). Rings constriction caused by ET-1 were attenuated in normal rats if the rings were immersed in the KH fluid with insulin ( P< 0.01), but no obvious changes were found in hyperglycemic rats.CONCLUSION: (1) the vasoconstriction of aortic rings caused by ET-1 can be reduced by hyperglycemia. (2) Insulin can attenuate the aortic response to ET-1. (3) Insulin can not attenuate the vasoconstriction caused by ET-1 in hyperglycemic rats. These results suggest that insulin may affect vasoconstriction caused by ET-1, which may be involved in the pathogenesis of vascular complication in diabetic or insulin resistance condition.     

Effect of Ginkgo biloba extract on cerebral ischemia during early stage of subarachnoid hemorrhage in rats

AIM: To investigate the effect of Ginkgo biloba extrac (GBE) on cerebral ischemia during early stage of subarachnoid hemorrhage (SAH). METHODS: Noncraniotomy models of SAH in Wistar rats were used and animals were divided into sham-operated group, SAH group and SAH+GBE group. Dynamic change of regional cerebral blood flow (rCBF) was detected. Brain endothelin-1(ET-1) and calcium contents were also determined at different time point during 24 hours after the operation. Pathological change of neurons of hippocampus CA1 region was observed. RESULTS: In SAH group, rCBF decreased immediately and persistently after induction of SAH. Values of brain ET-1 content and calcium content at 1 hour, 6 hours and 24 hours were significantly higher than those in sham-operated group. Neurons of hippocampus CA1 region were damaged severely 3 days after onset of SAH. Above abnormal changes in SAH+GBE group were much slighter than those in SAH group. CONCLUSION: GBE may relieve cerebral ischemic damage after SAH.