血管紧张素-（1-7）对野百合碱诱导的肺动脉高压和肺血管重构的影响

目的： 探讨血管紧张素-（1-7）［Ang-(1-7)］对野百合碱(MCT)诱导的肺动脉高压(PAH)模型中肺动脉压力和肺小动脉重构的影响。方法: 雄性Sprague-Dawley大鼠60只,随机分为:对照组、PAH组、PAH +Ang-(1-7)组。PAH 组和PAH+Ang-(1-7)组一次性颈部注射MCT60 mg/kg,24 h后经微泵持续泵入生理盐水或Ang-(1-7)(24 μg·kg-1·h-1)共4周。对照组一次性颈部注射相同体积的生理盐水,24 h后泵入生理盐水。4周后,测定大鼠的右室收缩压(RVSP)和右心室肥厚指数(RVHI),并运用图像分析软件,测定肺小动脉管壁厚度(WT)占动脉外径(ED)的百分比(WT %)及管壁面积(WA)占血管总面积的百分比(WA%)。通过放射免疫方法检测肺组织中一氧化氮(NO)浓度。 Western blotting分析肺组织内皮一氧化氮合酶(eNOS)和eNOS Ser1177-phosphorylation 的表达。 结果: PAH组与对照组相比,RVSP、RVHI、WT%、WA%明显升高（P<0.01）,肺组织中NO浓度、eNOS、eNOS Ser1177-phosphorylation 的表达水平显著降低（P<0.01）;Ang-(1-7)干预后RVSP、RVHI、WT%、WA %明显降低（P<0.01）,肺组织NO浓度、eNOS、eNOS Ser1177-phosphorylation 的表达明显升高（P<0.01）。结论: 在MCT诱导的肺动脉高压模型中,Ang-(1-7)可预防肺动脉高压的发生,同时抑制肺血管的重构,其机制可能与Ang-(1-7)升高肺组织NO浓度,上调eNOS的表达以及eNOS Ser1177-phosphorylation 水平有关。     

黄芩素对野百合碱诱导的肺动脉高压大鼠血管壁增厚的抑制作用

目的:观察黄芩素(baicalein)对野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary artery hypertension,PAH)大鼠的治疗作用,并初步探讨其机制。方法 :28只雄性SD大鼠随机分为对照组、MCT模型组、黄芩素低剂量组和黄芩素高剂量组。除对照组外,其余各组大鼠皮下注射MCT建立大鼠PAH模型,黄芩素低、高剂量组于MCT注射2周后分别灌胃黄芩素50和100 mg·kg~(-1)·d~(-1),持续14 d,对照组灌胃等量生理盐水。造模4周后,测定大鼠右心室收缩压(right ventricular systolic pressure,RVSP)、右心室肥厚指数(right ventricular hypertrophy index,RVHI)和右心室质量指数(right ventricular mass index,RVMI);Masson染色检测肺组织纤维化程度;HE染色观察肺血管病理形态学变化;Western blot测定各组肺组织α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)蛋白水平及肺小动脉p38、ERK和JNK的磷酸化水平。结果:与对照组比较,MCT模型组大鼠的RVSP、RVHI和RVMI均明显升高(P0.01),肺组织纤维化明显,肺组织中α-SMA表达上调(P0.01),肺动脉壁增厚,肺小动脉p38,ERK和JNK磷酸化水平明显升高(P0.01);与MCT模型组相比,黄芩素高、低剂量组的RVSP、RVHI和RVMI明显降低(P0.01),肺组织纤维化和血管壁增厚明显改善,p38、ERK和JNK的磷酸化水平减少(P0.01)。结论:黄芩素可减轻MCT诱导的肺动脉高压,其作用通过抑制肺动脉壁增厚来实现,其分子机制可能与其抑制肺动脉的MAPK信号通路有关。     

miR-124过表达对肺动脉高压大鼠右心重构的影响

目的:研究腺相关病毒(adeno-associated virus,AAV)介导的微小RNA-124(miR-124)过表达对野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠右心重构的作用。方法:32只健康雄性SD大鼠随机分为4组:正常对照(control)组、MCT+生理盐水(normal saline, NS)组、MCT+AAV-GFP (MCT+GFP)组和MCT+AAV-miR-124 (MCT+miR-124)组。后3组大鼠麻醉后经气管导管分别缓慢注入100μL NS、AAV-GFP和AAV-miR-124,3周后经腹腔注射MCT(60 mg/kg)建立PAH模型。测量大鼠右心室收缩压(RVSP)和平均动脉压,计算右心室肥厚指数(RVHI)和右心室重量指数(RVWI)。右心组织病理切片行天狼星红染色,观察心肌的病理改变。RT-qPCR检测miR-124在肺和右心组织中的表达水平。Western blot检测右心组织中转化生长因子β_1(TGF-β_1)和p-Smad2的表达水平。结果:与control组相比,MCT+NS和MCT+GFP组大鼠的RVSP、RVHI、RVWI、TGF-β_1表达和p-Smad2表达均显著增加(P0.05),右心室心肌细胞显著肥大,胶原沉积显著增多;与MCT+GFP组相比,MCT+miR-124组RVSP、RVHI、RVWI、TGF-β_1表达和p-Smad2表达均显著降低(P0.05),右心室心肌细胞肥大程度显著减轻,胶原沉积显著减少。结论:过表达miR-124可有效降低MCT诱导的大鼠RVSP,减轻右心重构,其机制可能与下调TGF-β_1和p-Smad2的表达有关。     

ACE2基因敲除小鼠止血带休克后肾组织ACE/AngⅡ表达的变化及其与肾损伤的关系

 目的： 通过观察血管紧张素转换酶2(ACE2)基因敲除(KO)小鼠止血带休克(TS)后肾组织血管紧张素转化酶/血管紧张素Ⅱ（ACE/AngⅡ）的表达及损伤程度的变化,探讨ACE2在休克后急性肾损伤中的作用。方法： 小鼠双下肢用止血带结扎缺血2 h、松带后再灌注4 h复制TS模型。将雄性6月龄野生型（WT）C57BL/6小鼠和相同背景的ACE2 KO小鼠各12只分为4组,即WT组、WT+TS组、KO组和KO+TS组,每组6只。Western blotting测肾组织ACE蛋白的表达;ELISA法测定肾组织AngⅡ表达;利用化学比色方法测定肾组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、血尿素氮（BUN）和血清肌酐（Cr）含量。结果： 与WT小鼠相比,WT+TS小鼠肾组织ACE/AngⅡ表达明显增加,出现肾组织氧化应激损伤和功能改变;与WT小鼠相比,KO小鼠肾组织ACE/AngⅡ表达增加,但未见明显的氧化应激损伤和功能变化;与WT+TS小鼠相比,KO+TS小鼠肾ACE/AngⅡ表达进一步增加,肾组织氧化应激和肾功能损伤明显加重。结论： ACE2基因缺失可能通过增加ACE/AngⅡ表达加重止血带休克肾的氧化应激损伤,针对ACE2靶f点的药物有可能成为防治止血带休克时急性肾损伤的策略之一。     

EGF和AngⅡ激活人肾上腺皮质癌H295R细胞ERK通路

目的研究表皮生长因子(EGF)和血管紧张素Ⅱ(AngⅡ)联合作用对肾上腺皮质癌H295R细胞的细胞外信号调节蛋白激酶(ERK)信号通路的影响。方法用不同剂量的EGF和AngⅡ刺激H295R细胞,或用特异性EGF受体酪氨酸激酶抑制剂AG1478预处理后再加入AngⅡ刺激细胞,用Western blot法检测磷酸化ERK1/2;EGF及AngⅡ单独或联合刺激细胞,检测ERK1/2、P90RSK和Bad的磷酸化水平。结果 EGF和AngⅡ均刺激细胞ERK1/2和P90RSK磷酸化,在刺激ERK1/2磷酸化上呈剂量依赖性,两者联合处理其激活ERK1/2和P90RSK的作用产生叠加,AngⅡ和EGF单独及联合处理细胞,ERK1/2磷酸化水平分别是对照组的6.3±1.4、2.2±0.6及10.1±1.1倍。AngⅡ刺激细胞Bad磷酸化,而EGF无此作用。AG1478不能阻断AngⅡ诱导的Erk1/2激活。结论EGF和AngⅡ明显激活H295R细胞的ERK信号通路,两者作用有叠加效应。     

Activation of ERK pathway by EGF and angiotensin Ⅱ in adrenocortical carcinoma H295R cells

目的 研究表皮生长因子(EGF)和血管紧张素Ⅱ(AngⅡ)联合作用对肾上腺皮质癌H295R细胞的细胞外信号调节蛋白激酶(ERK)信号通路的影响.方法 用不同剂量的EGF和Ang Ⅱ刺激H295R细胞,或用特异性EGF受体酪氨酸激酶抑制剂AG1478预处理后再加入AngⅡ刺激细胞,用Western blot法检测磷酸化ERK1/2;EGF及AngⅡ单独或联合刺激细胞,检测ERK1/2、P90RSK和Bad的磷酸化水平.结果 EGF和AngⅡ均刺激细胞ERK1/2和P90RSK磷酸化,在刺激ERK1/2磷酸化上呈剂量依赖性,两者联合处理其激活ERK1/2和P90RSK的作用产生叠加,AngⅡ和EGF单独及联合处理细胞,ERK1/2磷酸化水平分别是对照组的6.3±1.4、2.2±0.6及10.1±1.1倍.AngⅡ刺激细胞Bad磷酸化,而EGF无此作用.AG1478不能阻断AngⅡ诱导的Erk1/2激活.结论 EGF和AngⅡ明显激活H295R细胞的ERK信号通路,两者作用有叠加效应.     

复合离子盐对高血压大鼠肾脏皮质AngⅡ、NO的产生及磷酸化ERK1／2表达的影响

目的观察复合离子盐对自发性高血压大鼠（SHR）。肾脏皮质AngⅡ、NO的产生，及对磷酸化ERK1／2（p-ERK1／2）表达的影响，探讨复合离子盐对SHR。肾脏保护作用的可能机制。方法42只8周龄雄性SHR随机分为4组：8％食盐摄入组（HS组）；1％复合离子盐摄入组（CIS组）；1％复合离子盐＋2．25％L-精氨酸摄入组（CIS＋L-Arg组）；1％食盐摄入组（NS组），持续干预12周。干预期间定期观察大鼠血压、尿蛋白的变化；干预结束后处死动物，放射免疫法检测肾皮质中AngⅡ、NO含量；并通过Western-blot法分析SHR肾脏皮质磷酸化ERK1／2蛋白表达的情况。结果12周干预结束后，CIS组与CIS＋L-Arg组血压升高趋势明显低于Ns组（P〈0．01）。CIS组与CIS＋L-Arg组尿蛋白排泄量与实验前相比无差异，但显著低于Ns组（P〈0．01）。与Ns组相比，CIS组与CIS＋L-Arg组可明显促进SHR肾脏组织NO的生成（P〈0．01），抑制组织AngⅡ的产生（P〈0．01），同时p-ERK1的表达在CIS组与CIS＋L—Arg组明显降低（P〈0．05）。结论复合离子盐与普通食盐比较，长期同等量摄入时可通过改变。肾皮质中AngⅡ、NO含量，改善其功能平衡，还可使ERK1／2信号传导通路发生改变，这可能改善盐诱导的靶器官损害作用。     

肺动脉高压大鼠肺部炎症与CD4+ T 淋巴细胞上Cx40、Cx43 的相关性研究

目的:探讨肺动脉高压大鼠肺组织炎症的变化与CD4~+T淋巴细胞上连接蛋白(Cx) 40、43表达的相关性研究。方法:选取12周龄雄性SD大鼠12只,随机分为对照组和肺动脉高压(PAH)组,野百合碱(MCT)溶液一次性腹腔注射60 mg/kg,4周造模成功后,记录右心室肥厚指数(RVHI),HE染色观察大鼠肺脏病理学变化,ELISA方法检测肺组织中IL-6、TNF-α的表达,流式细胞术检测T淋巴细胞CD4/CD8的表达比率以及CD4~+T淋巴细胞上Cx40、Cx43的表达变化。结果:与对照组比较,PAH组右心室重量与RVHI升高; PAH组肺脏中小动脉血管壁增厚,炎性细胞浸润,PAH组大鼠肺中小型动脉的管壁厚度占血管外径的百分比(WT%)和肺动脉管壁面积与管总面积的百分比(WA%)均增高(P0. 05);肺动脉高压大鼠肺组织匀浆中细胞因子IL-6和TNF-ɑ表达水平上调(P0. 05); PAH组CD3~+T淋巴细胞比例升高(P 0. 05),PAH组CD4~+/CD8~+升高(P0. 05); PAH组CD4~+T淋巴细胞上Cx40、Cx43表达显著增高(P0. 01),肺组织匀浆中细胞因子IL-6、TNF-α与CD4~+T淋巴细胞上Cx40和Cx43高表达呈显著正相关(P0. 05)。结论:MCT诱导的肺动脉高压引起的肺部炎性改变可能与T淋巴细胞上连接蛋白表达增高有关。     

PKCζ与Raf在AngⅡ引起的大鼠血管平滑肌细胞ERK1／2活化中的作用水

目的：研究血管紧张素Ⅱ（AngⅡ）诱导大鼠血管平滑肌细胞（VSMC）肥大的信号转导途径中PKCζ与Raf的作用关系。方法：[^3H]-亮氨酸掺入反映VSMC蛋白质合成；Western blotting检测ERK1／2和PKCζ表达；免疫共沉淀实验检测信号分子间的相互作用。结果：AngⅡ刺激可引起VSMC[^3H]-亮氨酸掺入显著增加，PKC非特异性抑制剂和PKCζ假底物抑制剂（PS—PKCζ）均明显抑制AngⅡ引起的作用。PS—PKCζ预处理使AngⅡ刺激VSMC的ERK1／2磷酸化水平明显降低。转染dominant negative Raf（Raf S621A）质粒的VSMC中的PKCζ磷酸化水平与转染野生型Raf质粒无明显差异。AngⅡ刺激使Ras与Raf结合增加，但PKCζ抑制剂不影响AngⅡ引起的Raf与Ras的结合。转染Raf S621A抑制Raf活化后，AngⅡ引起的ERK1／2磷酸化水平降低。结论：在VSMC中，PKCζ亚型参与AngⅡ诱导的VSMC蛋白合成，但PKCζ可能通过非依赖Raf的途径激活ERK1／2。     

脂肪间充质干细胞对野百合碱诱发的肺动脉高压大鼠肺动脉钙离子通道的影响

 目的：探讨脂肪间充质干细胞(adipose tissue-derived mesenchymal stem cells,ADMSCs)移植对野百合碱（monocrotaline,MCT）诱发的肺动脉高压（pulmonary arterial hypertension,PAH）大鼠肺动脉钙离子通道的影响。方法：胶原酶消化法分离培养ADMSCs。雄性SD大鼠24只,分为正常对照组（Ctr组）、PAH组和ADMSCs组,每组8只。右心导管法测定大鼠的平均肺动脉压(MPAP);称重法测右心室肥厚指数（RVHI）;分别用RT-PCR及Western blotting法测定大鼠肺动脉干电压门控性钙离子通道α1c亚基（CaVα1c）肌浆/内质网Ca2+ ATP酶2a（SERCA-2a）、三磷酸肌醇受体1（IP3R-1）、瞬时受体电位通道1（TRPC1）和TRPC6 mRNA和蛋白的表达水平。结果：（1）MCT注射4周后,与Ctr组相比, PAH组大鼠MPAP和RVHI均显著升高（P<0.05）;ADMSCs移植2周后,与PAH组相比,ADMSCs组MPAP和RVHI均明显降低（P<0.05）。（2）与Ctr组相比,PAH组大鼠肺动脉CaVα1c、TRPC1和TRPC6 mRNA及蛋白表达水平均明显增强（P<0.05）,SERCA-2a 和IP3R-1 mRNA及蛋白表达水平均明显降低（P<0.05）;与PAH组相比,ADMSCs组CaVα1c、TRPC1和TRPC6的表达均明显降低（P<0.05）,SERCA-2a 和IP3R-1的表达均明显增强（P<0.05）。结论：ADMSCs能有效地降低MCT诱发的PAH大鼠的肺动脉压力,减轻右心室肥厚。ADMSCs降低肺动脉压力可能与钙离子通道变化有关。     

人参皂苷Rg2对野百合碱诱导肺动脉高压模型大鼠的作用

目的 探讨人参皂苷Rg2(ginsenoside-Rg2)对野百合碱(monocrotaline,MCT) 诱导的肺动脉高压(pulmonary arterial hypertension,PAH) 模型大鼠的作用.方法 将48只雄性SD 大鼠随机分为对照组、模型组、人参皂苷Rg2 (20、40、80 mg/kg) 组和波生坦(Bos,200 mg /kg) 组,每组8只.一次性腹腔注射MCT(50 mg/kg) 复制PAH 模型,此后按分组灌胃给药,每天1 次,连续28d.通过颈总动脉和右心室用八道生理记录仪测定右心室收缩压(right ventricle systolic pressure,RVSP)、平均动脉压(mean arterial blood pressure,MBP)、心率(heart rate,HR).处死动物后采集血浆测定内皮素-1(endothelin-1,ET-1)和一氧化氮(nitric oxide,NO)的水平并测定右心肥大指数.结果 野百合碱注射后第28天时,与对照组比较,模型组右心室压力、右心肥大指数明显升高,心率和平均动脉压明显减小;血浆ET-1水平明显增加,NO水平明显降低.人参皂苷Rg2能明显缓解这些变化.结论 人参皂苷Rg2对野百合就所致的肺动脉高压模型大鼠具有改善作用.     

Ang-(1-7)与肺高压状态下肺血管平滑肌细胞的增生

背景：Ang-(1-7)虽然具有抗血管平滑肌细胞增殖作用,但在不同的血管床中其作用可能存在差异。直接给予外源性Ang-(1-7)是否可抑制肺动脉高压大鼠肺血管平滑肌细胞的增殖尚不清楚。 目的：探讨Ang-(1-7)对野百合碱诱导的肺动脉高压大鼠肺血管平滑肌细胞增殖的影响。 方法：雄性SD大鼠颈部一次性注射60 mg/kg野百合碱制备肺动脉高压模型。24 h后,分别经微泵持续泵入Ang-(1-7)(治疗组)或生理盐水(模型组),并设立未造模的对照组。给药2,4周,测定大鼠的右心室收缩压、心室质量、肺小动脉管壁厚度占管径的百分比及管壁面积占血管总面积的百分比。免疫组织化学方法检测肺血管平滑肌细胞α-平滑肌肌动蛋白及增殖细胞核抗原的表达。 结果与结论：野百合碱诱导2周,与对照组比较,模型组大鼠右心室收缩压、各心室的质量无明显变化,肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率显著增高,α-平滑肌肌动蛋白显著降低;野百合碱诱导4周,模型组大鼠右心室收缩压、各心室的质量、肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率均显著增高,α-平滑肌肌动蛋白显著降低。而治疗组上述指标与对照组比较差异无显著性意义   (P > 0.05)。说明在野百合碱诱导的肺动脉高压模型中,在肺动脉压增高之前已有肺血管形态学的变化,Ang-(1-7)可通过减轻肺血管平滑肌细胞的增生抑制大鼠肺动脉压的升高。     

内皮祖细胞移植对肺动脉高压大鼠一氧化氮、内皮素的影响

目的研究同种异体内皮祖细胞（EPCs）移植对野百合碱（monocrotaline,MCT）所致肺动脉高压（Pulmonary Artery Hypertensinn,PAH）大鼠的影响,并观察肺动脉血一氧化氮（NO）、内皮素（ET）的变化,探讨其治疗PAH的机制。方法体外培养并鉴定大鼠EPCs,MCT诱发肺动脉高压模型组由尾静脉注入标记的EPCs。在移植EPCs后第21天,测定肺血流动力学参数,计算平均肺动脉压（mPAP）,分别用硝酸还原酶法,放射免疫法测定NO及ET-1值。结果与模型组（29．33±3．01）mm—Hg相比,EPCs治疗组（21．89±2．69）mmHg平均肺动脉压明显下降,肺动脉血的NO值明显增加,（49．28±5．31 vs 21．64±3．06）μmol／L（P〈0．05）,ET-1值由（354．40±36．35）pg／ml降至（259．20±29．08）pg／ml（P〈0．05）。结论同种异体EPCs移植可有效降低肺动脉压力,作用机制可能与其分化为血管内皮细胞,修复损伤的肺血管内皮,调节NO与ET-1的含量有关。     

氟西汀对野百合碱诱导Wistar大鼠肺动脉和右心室构型重建的影响

目的 研究氟西汀对野百合碱(monocrotaline,MCT)诱导Wistar大鼠肺动脉和右心室构型重建的影响.方法 应用野百合碱建立大鼠肺动脉高压模型,40只Wistar大鼠均分为4组:对照组(control)、模型组(MCT)、氟西汀低剂量2mg/kg组(MCT+F2)和氟西汀高剂量lOmg/kg组(MCT+F1...     

Ruscogenin exerts beneficial effects on monocrotaline-induced pulmonary hypertension by inhibiting NF-κB expression

This study aims to examine the effect of ruscogenin on pulmonary arterial hypertension (PAH) and to determine the mechanism underlying this effect. We isolated pulmonary vascular smooth muscle cells (PVSMCs) from the pulmonary artery of the rats; the PVSMCs were cultured in vitro and then were treated with platelet-derived growth factor (PDGF), PDGF + ruscogenin, or PDGF + ruscogenin + parthenolide. We randomized Sprague-Dawley rats into five groups as follows: control group, PAH group, low-dose group, medium-dose group, and high-dose group; the rats in the low-, medium-, and high-dose groups received the vehicle and ruscogenin 0.1, 0.4, and 0.7 mg/kg, respectively, from day 1 to day 21 after injection of monocrotaline (MCT). We measured the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), and medial wall thickness of the pulmonary artery (PAWT). We examined the levels of the nuclear factor kappa B (NF-κB) protein by using immunohistochemistry and western blot analysis, and the mRNA levels of NF-κB in PVSMCs were evaluated using real-time polymerase chain reaction (PCR). The mPAP, RVSP, and PAWT and the protein and mRNA levels of NF-κB were significantly higher in the PAH model group than in the control group (P < 0.05). Ruscogenin induced a significant dose-dependent decrease in the mPAP, RVSP, and PAWT and in the NF-κB expression in the PAH group (P < 0.05), which suggests that ruscogenin will also exert dose-dependent effects on MCT-induced PAH through the inhibition of NF-κB.     

Microvascular regeneration in established pulmonary hypertension by angiogenic gene transfer

Pulmonary arterial hypertension (PAH) is characterized by widespread loss of pulmonary microvasculature. Therefore we hypothesized that angiogenic gene therapy would reverse established PAH, in part restoring the lung microcirculation. Three weeks after monocrotaline (MCT) treatment, Fisher 344 rats were randomized to receive a total of either 1.5 x 10(6) syngeneic fibroblasts (FB) transfected with vascular endothelial growth factor A (VEGF), endothelial NO synthase (eNOS), or null-plasmid transfected FBs. Right ventricular systolic pressure (RVSP) was similarly increased in all MCT-treated groups at the time of gene transfer. Animals receiving the null-vector progressed to severe PAH by Day 35 (P < 0.001). In contrast, eNOS gene transfer significantly reduced RVSP at Day 35 compared with Day 21, whereas VEGF prevented further increases in RVSP over the subsequent 2 wk but did not reverse established PAH. RV hypertrophy was significantly reduced in both the eNOS-treated and VEGF-treated groups compared with the null-transfected controls. Fluorescent microangiography revealed widespread occlusion of the pre-capillary arterioles 21 d after MCT treatment, and animals receiving eNOS gene transfer exhibited the greatest improvement in the arteriolar architecture and capillary perfusion at Day 35. Cell-based eNOS gene transfer was more effective than VEGF in reversing established PAH, associated with evidence of regeneration of pulmonary microcirculation.     

Palosuran Treatment Effective as Bosentan in the Treatment Model of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p?<?0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p?=?0.001). Finally, 50–125-μm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p?<?0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p?<?0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.