Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,...Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.展开更多
To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia1...To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.展开更多
Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endoth...Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endothelial function [as indexed by big endothelin-1 （ET-1）] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF （P 〈 0.05）, both groups had higher hs-CRP level than controls （P 〈 0.05）. Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance （P 〉 0.05）, and both groups had higher big ET-1 levels than controls （P 〈 0.05）. Multiple regression analyses revealed hs-CRP as an inde- pendent determinant of AF （P 〈 0.001）. Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF （P 〈 0.001）, but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients （r = 0.563, P 〈 0.05）, however, the relationship in persistent AF patients was poor （r = 0.094, P 〈 0.05）. Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET- 1 level.展开更多
Plasma concentrations of endothelin in bloor from the femoral vein and the antecubital vein were measured in 35 patients with mitral stenosis and heart failure before and after percutaneous balloon mitralvalvuloplasty...Plasma concentrations of endothelin in bloor from the femoral vein and the antecubital vein were measured in 35 patients with mitral stenosis and heart failure before and after percutaneous balloon mitralvalvuloplasty(PBMV). The basal plasma concentrations of endothelin in blood from the antecubirtal vein in the patients were significantly higher than those in 32 control subjects (15. 40± 3. 32 vs. 9. 59± 2. 66 pg/ml, P<0. 001). Plasma endothelin concentrations in patients in New York Heart Association functional classes Ⅱ and Ⅲ were significantly higher than those in control subjects, respectively. The concentrations of endothelin in patients with atrial fibrillation were also significantly higher than those in patients with normal sinus rhythm. Ten to fifteen minutes after PBMV, plasma endothelin concentrations in blood from the femoral vein significantly decreased from 16. 14 ± 3. 34 to 13. 74 ± 3. 78 pg/ml (P<0. 01 ). Seventy-two hours after the procedure, the concentrations of endothelin in blood from the antecubital vein had fallen to 12. 31 ± 2. 55 pg/ml (P<0. 001 vs. before PBMV and control subjects). Plasma endothelin concentrations still tended to be higher in patients with atrial fibrillation than those in normal sinus rhythm, but the difference did not reach statistical significance. There were weak but significantly correlations of plasma endothe lin concentrations with the mean left atrial pressure (r= 0. 424 , P < 0.001 ), mean right atrial pressure (r=0. 323, P<0. 01), mean transmitral pressure gradient (r= 0. 397, P<0. 001), heart rate (r= 0. 350,P<0. 005)and mitral valve area (r=-0. 454, P<0. 001) in the patients before and after PBMV.展开更多
Radioimmunoassays were used to measure the concentration changes of plasma endothelin(ET) and atrial natriuretic peptide(ANP) during the onset and after termination of paroxysmal supraventricular tachycardia(SVT). 30 ...Radioimmunoassays were used to measure the concentration changes of plasma endothelin(ET) and atrial natriuretic peptide(ANP) during the onset and after termination of paroxysmal supraventricular tachycardia(SVT). 30 cases were reviewed and compansons with 42 normal subjects were made. There are very significant differences(P<0.0001) in the concentration changes of both plasma ET and ANP during the onset and 30 minutes after the termination of SVT. During the onset period of SVT. the plasma ET and ANP were markedly elevated and 30 minutes after its termination they were lowered significantly, but their concentrations were still 2-fold higher than ihose of the control group. As the biological effects of ANP and ET are antagonistic to each other. their parallel elevation and lowering of plasma concentrations during and.after the termination of SVT reveal that these 2 hormones parucipate in the pathophysiological process of SVT. This phenomenon is possibly one of the homeostatic regulatory functions in the organism.展开更多
A model of cerebral vasospasm (CVS) associated with subarachnoid hemorrhage (SAH) was prepared on male Sprague-Dawley rats by a single intracisternal injection (i. c.) of 150 μl autologous fresh blood directly to Wil...A model of cerebral vasospasm (CVS) associated with subarachnoid hemorrhage (SAH) was prepared on male Sprague-Dawley rats by a single intracisternal injection (i. c.) of 150 μl autologous fresh blood directly to Willis circle.The process of CVS was monit展开更多
Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Meth...Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET- 1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET- 1 levels increased significantly on week 2 and week 4 of pressure overload. ET- 1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41％ (P< 0.01) and 65％ (P< 0.01) in sarcolemma in H- 2 week and H- 4 week groups, but was decreased by 24％ (P< 0.01) and 21％ (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33％ (P< 0.01) and 57％ (P< 0.01) in group H- 2 week and H- 4 week, respectively. Conclusion. ET- 1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.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
objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enric...objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enriched substrates (1. 0 mmol/L [3-13C] lactate and 0. 25 mmol/L [1,2~13C ] acetate) ; ET-1 was added to the perfusate to produce an estimated circulating concentration of 6O pmol/L (ET60) or 600 pmol/L (ET600). Myocardial energy metabolism and substrate utilization were analyzed by multi-nuclear (31P and 13 C) magnetic resonance (NMR) spectroscopy. Meantime, cardiac output (CO), coronary flow (CF) and left ventricular developed pressure (LVDP) were recorded (Millar catheter). Results: CT decreased when ET-1 level enhanced (- 30% for ET60 group and - 42% for ET600 group,Pr0. 05). CO transiently increased above control but fell after 35 min infusion (-4% in ET60 group and - 23% in ET600 group respectively,P <0. 05). LVDP was also decreased at the end of ET per fusions. 31P NMR spectroscopy showed a decrease in cellular phosphorylation potential ([ATP]/[ADP][Pi]) when ET-1 level increased (y= 5. 2303e-2-5. 517le 5x R ~ 2= 0. 885). However, It is interesting that the PCr/ATP ratio decreased only in ET6O group, while in ET6oo group the further decrease of [ATP]/[ADP][Pi] did not company a further decrease in PCr/ATP. This phenomenon may suggest an inhibition of CPK activity under the circumstance of high ET-1 level. 13C NMR spectroscopy showed an ET-1 mediated inhibition on exogenous lactate utilization. Conclusion: (1)En dothelin-1 has either a directly positive inotropic effect on isolated perfused rat hearts or an indirectly negative inotropic effect through reduced coronary flow; (2)High level ET-1 may decrease myocardial phosphorylation potential and inhibit CPK activity as well ; (3)Acetate is a better substrate comparing to lactate for myocardium of the patients with increased systemic ET levels.展开更多
Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats we...Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)展开更多
基金National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020013)CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-049)。
文摘Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.
文摘To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.
文摘Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endothelial function [as indexed by big endothelin-1 （ET-1）] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF （P 〈 0.05）, both groups had higher hs-CRP level than controls （P 〈 0.05）. Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance （P 〉 0.05）, and both groups had higher big ET-1 levels than controls （P 〈 0.05）. Multiple regression analyses revealed hs-CRP as an inde- pendent determinant of AF （P 〈 0.001）. Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF （P 〈 0.001）, but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients （r = 0.563, P 〈 0.05）, however, the relationship in persistent AF patients was poor （r = 0.094, P 〈 0.05）. Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET- 1 level.
文摘Plasma concentrations of endothelin in bloor from the femoral vein and the antecubital vein were measured in 35 patients with mitral stenosis and heart failure before and after percutaneous balloon mitralvalvuloplasty(PBMV). The basal plasma concentrations of endothelin in blood from the antecubirtal vein in the patients were significantly higher than those in 32 control subjects (15. 40± 3. 32 vs. 9. 59± 2. 66 pg/ml, P<0. 001). Plasma endothelin concentrations in patients in New York Heart Association functional classes Ⅱ and Ⅲ were significantly higher than those in control subjects, respectively. The concentrations of endothelin in patients with atrial fibrillation were also significantly higher than those in patients with normal sinus rhythm. Ten to fifteen minutes after PBMV, plasma endothelin concentrations in blood from the femoral vein significantly decreased from 16. 14 ± 3. 34 to 13. 74 ± 3. 78 pg/ml (P<0. 01 ). Seventy-two hours after the procedure, the concentrations of endothelin in blood from the antecubital vein had fallen to 12. 31 ± 2. 55 pg/ml (P<0. 001 vs. before PBMV and control subjects). Plasma endothelin concentrations still tended to be higher in patients with atrial fibrillation than those in normal sinus rhythm, but the difference did not reach statistical significance. There were weak but significantly correlations of plasma endothe lin concentrations with the mean left atrial pressure (r= 0. 424 , P < 0.001 ), mean right atrial pressure (r=0. 323, P<0. 01), mean transmitral pressure gradient (r= 0. 397, P<0. 001), heart rate (r= 0. 350,P<0. 005)and mitral valve area (r=-0. 454, P<0. 001) in the patients before and after PBMV.
文摘Radioimmunoassays were used to measure the concentration changes of plasma endothelin(ET) and atrial natriuretic peptide(ANP) during the onset and after termination of paroxysmal supraventricular tachycardia(SVT). 30 cases were reviewed and compansons with 42 normal subjects were made. There are very significant differences(P<0.0001) in the concentration changes of both plasma ET and ANP during the onset and 30 minutes after the termination of SVT. During the onset period of SVT. the plasma ET and ANP were markedly elevated and 30 minutes after its termination they were lowered significantly, but their concentrations were still 2-fold higher than ihose of the control group. As the biological effects of ANP and ET are antagonistic to each other. their parallel elevation and lowering of plasma concentrations during and.after the termination of SVT reveal that these 2 hormones parucipate in the pathophysiological process of SVT. This phenomenon is possibly one of the homeostatic regulatory functions in the organism.
文摘A model of cerebral vasospasm (CVS) associated with subarachnoid hemorrhage (SAH) was prepared on male Sprague-Dawley rats by a single intracisternal injection (i. c.) of 150 μl autologous fresh blood directly to Willis circle.The process of CVS was monit
基金the National Major Basic Research Program(No.G2000056905)
文摘Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET- 1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET- 1 levels increased significantly on week 2 and week 4 of pressure overload. ET- 1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41％ (P< 0.01) and 65％ (P< 0.01) in sarcolemma in H- 2 week and H- 4 week groups, but was decreased by 24％ (P< 0.01) and 21％ (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33％ (P< 0.01) and 57％ (P< 0.01) in group H- 2 week and H- 4 week, respectively. Conclusion. ET- 1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.
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objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enriched substrates (1. 0 mmol/L [3-13C] lactate and 0. 25 mmol/L [1,2~13C ] acetate) ; ET-1 was added to the perfusate to produce an estimated circulating concentration of 6O pmol/L (ET60) or 600 pmol/L (ET600). Myocardial energy metabolism and substrate utilization were analyzed by multi-nuclear (31P and 13 C) magnetic resonance (NMR) spectroscopy. Meantime, cardiac output (CO), coronary flow (CF) and left ventricular developed pressure (LVDP) were recorded (Millar catheter). Results: CT decreased when ET-1 level enhanced (- 30% for ET60 group and - 42% for ET600 group,Pr0. 05). CO transiently increased above control but fell after 35 min infusion (-4% in ET60 group and - 23% in ET600 group respectively,P <0. 05). LVDP was also decreased at the end of ET per fusions. 31P NMR spectroscopy showed a decrease in cellular phosphorylation potential ([ATP]/[ADP][Pi]) when ET-1 level increased (y= 5. 2303e-2-5. 517le 5x R ~ 2= 0. 885). However, It is interesting that the PCr/ATP ratio decreased only in ET6O group, while in ET6oo group the further decrease of [ATP]/[ADP][Pi] did not company a further decrease in PCr/ATP. This phenomenon may suggest an inhibition of CPK activity under the circumstance of high ET-1 level. 13C NMR spectroscopy showed an ET-1 mediated inhibition on exogenous lactate utilization. Conclusion: (1)En dothelin-1 has either a directly positive inotropic effect on isolated perfused rat hearts or an indirectly negative inotropic effect through reduced coronary flow; (2)High level ET-1 may decrease myocardial phosphorylation potential and inhibit CPK activity as well ; (3)Acetate is a better substrate comparing to lactate for myocardium of the patients with increased systemic ET levels.
文摘Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)
