Endothelin receptor antagonists for the treatment of diabetic nephropathy:A meta-analysis and systematic review

BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel and beneficial drug for DN,no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.AIM To assess the effectiveness and safety of ER antagonists among patients with DN.METHODS The EMBASE,PubMed,MEDLINE,Cochrane,and ClinicalTrials.gov databases were searched without any language restrictions.Relative risks with 95%confidence intervals(CIs)for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software.Publication bias was assessed using Egger’s test with Stata/SE software.RESULTS We enrolled seven studies with six data sets and 5271 participants.The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40%reduction in urinary albumin-to-creatinine ratio than the control group(P<0.0001 and P=0.02,respectively).Subgroup analysis for reductions in estimated glomerular filtration rate(eGFR)showed that for the middle-dosage subgroup,the ER antagonists group exhibited lower eGFR reduction than the control group(P<0.00001;mean difference,0.7095%CI:0.66,0.74).Moreover,significant reductions in systolic and diastolic blood pressure were observed in the invention group.CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor/angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR.However,attention should be given to adverse events,including cardiac failure,anemia,and hypoglycemia,as well as serious adverse events.

Effects of endotoxin on endothelin receptor in hepatic and intestinal tissues after endotoxemia in rats

INTRODUCTIONEndothelins(ETs) has a potent and sustainedvasoconstrictive effect on a variety of blood vessels.The vascular smooth muscle cell (VSMC)is thetarget for ETs.VSMC of the whole body containsendothelin receptor (ETR).A great number ofexperiments have shown that three distinctcomplementary DNAs of ETR have been identifiedi.e.,endothelin A receptor(ET_A receptor),endothelin B receptor(ET_B receptor)

Increased endothelin receptor B and G protein coupled kinase-2 in the mesentery of portal hypertensive rats

AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.

安立生坦治疗IgA肾病的疗效及安全性分析

目的探讨安立生坦作为选择性内皮素受体拮抗剂(endothelin receptor antagonist,ERA)在IgA肾病(IgA nephropathy,IgAN)患者中的疗效和安全性。方法收集北京大学第一医院肾内科2022年11月─2023年12月接受安立生坦治疗的IgA肾病患者的病历资料和随访数据,并在第4、8和12w时进行随访评估。研究的主要结果是随时间变化的24h尿蛋白、24h尿蛋白变化率、估算肾小球滤过率(estimate glomerular filtration rate,eGFR),同时监测药物的安全性。结果共纳入了147例IgA肾病患者。基线24h尿蛋白水平为1.16(0.74,1.99)g/d,安立生坦治疗后第4、第8、第12w的尿蛋白水平分别低于基线水平(Z=-8.157、-5.866、-5.238,均P<0.001)。在不同性别、eGFR分组、合并用药包括激素、免疫抑制剂、肾素-血管紧张素-醛固酮系统抑制剂(renin-angiotensin-aldosterone system inhibitor,RAASi)等亚组中,24h尿蛋白下降率无统计学差异(均P>0.05)。在12w随访期间,eGFR保持稳定。安立生坦在随访患者中耐受性良好,2例患者因水肿或肝功能损害停药。结论安立生坦可以降低IgA肾病患者尿蛋白且安全性良好。

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

The Expression of Endothelin Receptor B in Melanoma Cells A375 and Sk-mel-1 and the Proliferative Effects of Endothelin 3 on A375 Cells

In order to investigate the expression of endothelin receptor B （ETR-B） in human malignant melanoma （MM） cells A375 and SK-mel-1 and the proliferative effects of endothelin 3 （ET3） on A375 cells, RT-PCR was applied to detect the expression of ETR-B gene in human MM cells A375 and SK-mel-1. MTT method was used to evaluate the growth enhancing effects of ET3 on A375 cell line in vitro. The results showed that ETR-B gene was expressed in both MM A375 and SK-mel-1 cells. ET3 had stronger ability to enhance the proliferation of A375 cells in vitro in a concentration-dependent manner. It was suggested that ET3/ETR-B might play an important proliferative role in MM.

Correlation of calcitonin gene-related peptide and endothelin receptor A with subarachnoid hemorrhage

Numerous studies have demonstrated that endothelin-1 combines with endothelin receptor A, resulting in intense vasoconstriction. Although calcitonin gene-related peptide （CGRP） suppresses endothelin-1, CGRP and endothelin receptor A exhibit direct biological effects on brain tissue. The present study analyzed CGRP and endothelin receptor A expression following subarachnoid hemorrhage in rabbits using immunohistochemistry. CGRP expression was significant at 5 days after model establishment, and endothelin receptor A expression was significant at 3 days after model induction. The perimeter of the basilar artery was measured to determine the amount of cerebral vasospasm. Analytical results revealed a significantly shortened basilar artery perimeter following subarachnoid hemorrhage. Changes in the basilar artery perimeter were negatively associated with endothelin receptor A expression, but positively correlated with CGRP expression in vessels. These results suggest that following subarachnoid hemorrhage, CGRP and endothelin receptor A expressions dynamically changed in brain vessels and tissues, although these changes were not synchronous. Changes in endothelin receptor A expression exhibited a significant effect on the occurrence and development of delayed cerebral vasospasm and delayed neuronal death, while CGRP relaxed vessels and protected nerves.

Increased Expression of Endothelin Receptors in Human Cirrhosis—— Relationship with Splanchnic Hemodynamics

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (P p), portal blood flow quantity (Q p) and ET A and ET B receptor mRNA expression in human cirrhosis. In situ hybridization and reverse transcription polymerase chain reactions (RT PCR) were performed to determine the expression of ET A and ET B receptor mRNA in liver tissues from traumatic subjects ( n =10) and cirrhotic patients ( n =15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ET A receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ET B receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ET A and ET B receptor mRNA and P p and Q p in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ET A and ET B receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.

Correlation between Pulmonary Endothelin Receptors and Alveolar-arterial Oxygen Gradient in Rats with Hepatopulmonary Syndrome

The correlation between pulmonary endothelin receptors and alveolar-arterial oxygen gradient （A aDO2） in rats with hepatopulmonary syndrome was investigated. Animals were divided into 2 groups： Sham operated （Sham） group and common bile duct ligation （CBDL） group. Arterial blood gas was evaluated by a blood gas analyzer. The concentrations of ET-1 in blood and lung tissue sample were evaluated by radioimmunoassay. The distribution and expression of two kinds of subtype receptor of ET-1, ETRA and ETRB were examined by in situ hybridization. The results showed that the level of A aDO2, was higher in CBDI. group than that in Sham group （P〈0.05）. The levels of plasma and pulmonary ET-1 in CBDL group were both higher than in Sham group （P〈0.05 ）. There was no significant difference in average A of ETRA between two groups by imaging analysis （0.21±0.06 vs 0.22±0.08, P〉0.05）, while that of ETRB was higher in CBDI. group than in Sham group （0.58±0.16 vs 0.28±0.07, P〈0.05）. The expression of ETRBinlung was positively correlated with A aDO2（P〈0.05）. It was concluded that the widened A-aDO2 may be related with enhancement of the expression of ETRB in lung.

MUTATION OF THE ENDOTHELIN-B RECEPTOR AND THE ENDOTHELIN-3 GENE IN CHINESE SPORADIC CASES OF HIRSCHSPRUNG'S DISEASE

Objective To investigate the mutation of endothelin receptor B (EDNRB) gene and endothelin 3 (EDN 3) gene in sporadic Hirschsprungs disease (HD) in Chinese population. Methods Genomic DNA was extracted from bowel tissues of 34 unrelated HD patients which were removed by surgery. Exon 3, 4, 6 of EDNRB gene and Exon 1, 2 of EDN 3 gene were amplified by polymerase chain reaction (PCR) and analyzed by single strand conformation polymorphism (SSCP).Results EDNRB mutations were detected in 2 of the 13 short segment HDs. One mutant was in the exon 3; the other one was in the exon 6. EDN 3 mutation was detected in 1 of the 13 short segment HDs and in the exon 2. Both EDNRB mutation and EDN 3 mutation were detected in one short segment HD. No mutations were detected in the ordinary or long segment HD. Conclusion The mutations of EDNRB gene and EDN 3 gene are found in the short segment HD of sporadic Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene and EDN 3 gene play important roles in the pathogenesis of HD. the mutations of EDNRB and EDN 3 lead to the maldevelopment of the enteric nervous system.

Synthesis and Crystal Structure of an Endothelin Receptor Antagonist Ambrisentan

The title compound was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. The crystal is of orthorhombic system （C22H22N2O4, Mr = 378.42）, space group P2121 with a = 6.8786（12）, b = 14.259（2）, c = 19.712（3） A, V= 1933.5（6） A3, Z = 4, Dc = 1.300 g/cm3, f（000） = 800, μ= 0.090 mm-1, the final R = 0.0324 and wR = 0.0775 for 2410 observed reflections （I 〉 2σ（I））. The structure, especially the absolute configuration, of the title compound ambrisentan, an important endothelin receptor antagonist, was confirmed by single- crystal X-ray diffraction. The three aromatic rings in the lattice are basically orthogonal to one another. There is an intermolecular hydrogen bond in the crystal, which helps to further stabilize the crystal. One of the two non-classical intramolecular hydrogen bonds can help to stabilize the molecular conformation in the lattice.

Therapeutic Trial of an Endothelin Receptor Agonist for the Highly Pathogenic Avian Influenza A/H5N1 Virus Infection in Chicks

The rapid spread of the highly pathogenic A/H5N1 avian influenza virus among domestic birds and its transmission to humans has induced world-wide fears of a new influenza pandemic. A/H5N1 has infected over 300 people since 1997, and has shown a mortality rate of over 50%. The high mortality in human cases is thought to be enhanced by the excessive secretion of various endogenous factors, including cytokines and interleukins, stimulated by viral infections. Chickens infected with A/H5N1 viruses experience sudden death without showing severe clinical symptoms or inflammation. However, severe hemorrhage and congestion are seen in various tissues in sporadic chicken cases of A/H5N1-infections, especially in the pulmonary tissues, thus indicating that there is ischemia due to vascular abnormalities. Our previous studies have focused on the expression pattern of endothelin-1, which modulates the vascular tone via endothelin receptors. An Indonesian sporadic strain of A/H5N1 virus was intranasally administered to 10-day-old chicks, and the expression of endothelin was examined in the infected birds. All birds died within five days of inoculation, and had moderate inflammation accompanied by severe hemorrhage and congestion in the lungs. Immunohistochemical studies showed enhanced expression of endothelin-1 in the infected lungs. In addition, the real-time PCR analyses revealed that endothelin-1 and endothelin receptor A mRNA were significantly elevated in the birds with A/H5N1 infections. Subsequently, H5N1-infected birds were inoculated with bosentan hydrate, a competitive antagonist of endothelin receptors. Interestingly, the mortality rate of the infected birds was dramatically decreased in a dose-dependent manner by the administration of bosentan hydrate. The pathological lesions, including congestion and hemorrhage in the pulmonary tissues, were clearly inhibited. These findings are promising, and suggest that endothelin receptor antagonists are a potential treatment for the highly pathogenic avian flu.

INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN- 1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHY

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.

EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

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 .

治疗难治性高血压的新药:aprocitentan

aprocitentan(商品名:Tryvio)是一种口服给药的靶向双重内皮素A/B受体(ETA/ETB)拮抗剂,2024年3月19日获美国食品药品监督管理局批准上市,与其他抗高血压药物联合用于治疗成人难治性高血压。该文通过对aprocitentan的作用机制、药物代谢动力学、临床研究、不良反应、特殊人群用药及注意事项的文献查阅,意在为临床治疗难治性高血压提供用药参考。

基于美国FAERS和日本JADER数据库的内皮素受体拮抗剂不良事件信号分析

目的 分析马昔腾坦、安立生坦和波生坦不良事件发生特点,为临床选择内皮素受体拮抗剂提供参考。方法 基于美国食品药品监督管理局(FDA)不良事件报告系统(adverse event reporting system, FAERS)和日本药品不良事件报告数据库(Japanese adverse drug event report database,JADER)中2013年10月1日至2023年12月31日以马昔腾坦、安立生坦、波生坦为首要怀疑药品的所有不良事件报告,采用ROR法和IC法对内皮素受体拮抗剂相关不良事件信号进行计算,筛选阳性信号进行对比分析。采用Log-rank检验和非参数检验比较内皮素受体拮抗剂相关不良事件诱发时间差异性。结果 基于2个数据库共获得马昔腾坦不良事件报告35 150例、安立生坦75 177例、波生坦22707例。马昔腾坦、安立生坦的诱发贫血在JADER中报告数量最多,马昔腾坦、安立生坦、波生坦诱发液体潴留在FAERS中报告数量最多。波生坦肝功能异常相关信号强度显著高于马昔腾坦和安立生坦。马昔腾坦贫血相关不良事件信号强度显著高于安立生坦和波生坦。安立生坦液体潴留相关信号强度显著高于马昔腾坦和波生坦。对未成年患者进行不良事件信号挖掘发现,波生坦相较其他内皮素受体拮抗剂更容易诱发未成年患者肝功能检验异常,安立生坦更容易诱发未成年患者鼻咽不适。未成年患者使用马昔腾坦应重点关注贫血、血小板降低、肝功能指标异常、鼻衄、血压降低、低钾血症。马昔腾坦联合一氧化氮受体拮抗剂[173(IQR 40~544)]不良事件诱发时间最短,波生坦联合前列环素受体拮抗剂[632.5(IQR 222.75~1225.5)]不良事件诱发时间最长。结论 不同内皮素受体拮抗剂不良事件风险信号强度和不良事件诱发时间可能存在差异。对患者应开展个体化用药和监护,减少可能的不良反应,保障患者用药安全。

基于FAERS数据库的内皮素受体拮抗剂肺炎不良事件的信号挖掘

目的挖掘和分析内皮素受体拮抗剂发生肺炎相关不良事件(ADE)的信号,为临床安全用药提供参考。方法基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库,提取2015第1季度至2023第1季度数据,采用报告比值比、比例报告比、贝叶斯置信传播神经网络和多项泊松收缩器进行挖掘。结果提取到以内皮素受体拮抗剂为主要怀疑对象的肺炎相关ADE报告7279份,其中安立生坦3705份,波生坦1028份,马昔腾坦2546份。挖掘到与内皮素受体拮抗剂相关的肺炎ADE有68个,其中安立生坦21个,波生坦25个,马昔腾坦22个。采用ADE信号判定标准,形成信号的ADE共有14种,系统器官分类与累及系统均为感染及侵染类疾病。ADE中以感染性肺炎占比最高(93.61%),造成的死亡结局也最多。结论真实世界中内皮素受体拮抗剂会发生肺炎相关ADE。女性、高龄和高剂量是发生肺炎ADE的重要因素。这提示医疗人员在使用内皮素受体拮抗剂时,需要根据患者生理状态和药物特点个体化用药,保障用药安全。

内皮素受体拮抗剂CPU0213的生物活性及抑制ETA及ETB受体的作用(英文)

目的从合成的77个新化合物中经过生物活性筛选后得到新内皮素受体拮抗剂CPU0213。方法采用功能性抑制大鼠去内皮胸主动脉收缩及心肌ETA、ETB亚型放射受体结合实验。结果CPU0213抑制ETA及ETB受体作用最强,ETA及ETB的pA2分别为(8.52±0.26)及(7.28±0.04),放射受体分析的IC50,ETA及ETB分别为(2.57±1.41)及(95±34)nmol/L。结论CPU0213的对受体的作用强度及选择性优于Bosentan(与文献比较)。

烧冲复合伤早期肺组织ET-1及ETAR转录表达的研究

目的：探讨内皮素－１（ＥＴ－１）、内皮素Ａ型受体（ＥＴＡＲ）及肿瘤坏死因子α（ＴＮＦα）在烧冲复合伤病理生理过程中的作用和地位。方法：应用放射免疫及原位杂交和斑点杂交等核酸分子生物学技术，观测大鼠烧伤和烧冲复合伤后肺组织ＥＴ－１、ＥＴＲ及ＴＮＦα的转录表达变化、相互关系及与组织细胞损伤的关系。结果：伤后早期肺组织ＴＮＦα及ＥＴ－１的ｍＲＮＡ转录及其产生分泌均显著增加，血浆一氧化氮（ＮＯ）也有所增加，肺组织中的内皮素Ａ型受体（ＥＴＡＲ）ｍＲＮＡ升高，但ＥＴＲ却“下调”，各项指标变化均以烧冲复合伤组为显著，并与肺组织病理变化相关。结论：ＥＴ－１及其受体ＥＴＡＲ等在烧冲复合伤后肺的病理生理过程中可能起着重要作用。

黄芪对压力过载性左室肥厚大鼠心肌ETA，ETB表达的影响

目的观察黄芪对大鼠压力过载性心肌肥厚的逆转作用,并探讨不同剂量黄芪对肥厚心肌中内皮素受体(ETA、ETB)表达的影响。方法采用狭窄腹主动脉法制备压力过载性心肌肥厚模型。90只大鼠随机分为假手术组,模型组,低、中、高剂量黄芪组和卡托普利组,造模后第13周开始灌胃给药,连续12周。测定各组大鼠心重指数(heart weight index,HWI)及左室重量指数(lef tventricular weight index,LVWI),并采用RT-PCR、Westernblot方法检测心肌肥厚大鼠左室组织ETA、ETB的表达。结果黄芪呈剂量依赖性抑制模型大鼠左室重量指数的增加(P<0.01,P<0.001);各组间ETA、ETB mRNA表达无明显差异;与假手术组相比,模型组大鼠左心室ETA、ETB蛋白表达明显增加(P<0.05),高剂量黄芪抑制模型大鼠左室组织中ETA,ETB蛋白的表达(P<0.05,P<0.01)。结论黄芪抑制压力过载性大鼠左室肥厚,且能下调心肌组织ETA,ETB表达。