自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的 观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用.方法 雄性SHR 1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照.采用RBP-Ⅰ型大鼠血压心率测定仪测量大鼠尾动脉收缩压(SBP);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法 测定肾脏ACE2蛋白的表达水平.结果 1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定.2)SHR和WKY肾脏ACE2蛋白和mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和mRNA水平均低于同龄的WKY.S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反.结论 1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低.2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异.     

自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2) mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用。方法雄性SHR1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照。采用RBP-Ⅰ型大鼠血压心率测定仪测量大鼠尾动脉收缩压(SBP);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法测定肾脏ACE2蛋白的表达水平。结果1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定。2)SHR和WKY肾脏ACE2蛋白和 mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和 mRNA水平均低于同龄的WKY。S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反。结论1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低。2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异。     

ACE2和ACE在自发性高血压大鼠心肌中的变化

目的:观察自发性高血压大鼠(SHR)心肌的血管紧张素转化酶(ACE)和ACE2的表达,以探讨ACE2和ACE在高血压发生发展中的变化。方法:取15只SHR,处死,分离左心室,行RT-PCR、Western blot蛋白质免疫印迹和免疫组织化学检测ACE及ACE2表达;同步取10只WKY大鼠作为正常血压对照组。结果:SHR组心肌ACE的mRNA和蛋白质表达都显著高于WKY组[(1.68±0.34)∶(0.33±0.12),P<0.05;(1.21±0.14)∶(0.71±0.11),P<0.05],而ACE2的mRNA和蛋白质表达皆明显低于WKY组[(0.50±0.15)∶(1.16±0.24),P<0.05;(0.71±0.24)∶(1.22±0.14),P<0.05)]。免疫组织化学染色显示,SHR组ACE的阳性率明显高于WKY组(87%∶50%,P<0.05),而ACE2的阳性率明显低于WKY组(27%∶70%,P<0.05)。结论:SHR心肌ACE明显升高,ACE2显著降低;SHR高血压发生发展过程中存在着ACE和ACE2表达的失衡。     

缬沙坦对自发性高血压大鼠血管中血管紧张素转化酶2 mRNA表达的影响

目的:观察血管紧张素转化酶2(ACE2)在自发性高血压大鼠(SHR)血管中的表达以及缬沙坦对ACE2mRNA表达的影响。方法:24只12周龄雄性SHR随机分为SHR组和缬沙坦组,每组各12只,另设12只同龄雄性血压正常的Wistar大鼠作为对照组。缬沙坦组大鼠给予缬沙坦30mg.kg-1.d-1灌胃,SHR组及对照组给予等量0.9%氯化钠溶液灌胃。10周后,截取胸主动脉,光镜观察血管的病理变化,测定中膜厚度与血管腔内径之比;采用RT-PCR和免疫组织化学法检测胸主动脉中ACE2的表达。结果:与对照组比较,SHR组血管壁明显增厚,管腔变窄,且血管中ACE2mRNA和蛋白的表达均下调;而缬沙坦组ACE2mRNA和蛋白的表达明显高于SHR组。结论:高血压时血管重构可能与ACE2的表达下调有关,缬沙坦可能通过增加血管中ACE2的表达而发挥保护血管的作用。     

高血压大鼠ACE2的表达及其与一氧化氮相关性分析

目的探讨血管紧张素转换酶2(ACE2)在自发性高血压大鼠(SHR)中的表达情况并对其与血清一氧化氮(NO)水平作相关性分析.方法分别采用实时荧光定量PCR,Northern印迹以及免疫印迹技术测定心、肾组织中ACE2的mRNA与蛋白表达情况,同时用硝酸还原酶法检测血清NO含量.结果与WKY对照组相比,SHR大鼠心、肾组织中ACE2的mRNA和蛋白表达均明显下降(ACE2/GAPDH mRNA拷贝数比值为心脏0.043±0.012 vs 1.291±0.619;肾脏0.051±0.016 vs 0.914±0.433,P均<0.01;蛋白相对OD值为心脏0.729±0.046 vs 1±0.053;肾脏0.734±0.063 vs 1.005±0.05,P均<0.01),同时出现血清NO浓度下降[(24.3±8.0 vs 78.4±27.9)μmol/L,P<0.01).相关分析发现,大鼠血清NO水平与心、肾组织中ACE2/GAPDH的mRNA拷贝数比值呈正相关(r=0.610, 0.521,P均<0.05),而与血压水平则呈负相关(r=-0.656,P<0.05).结论 SHR大鼠心、肾组织中ACE2的mRNA和蛋白表达均明显下降,很可能与体内NO水平降低及血压上升有关.特异性影响ACE2转录和表达的药物将对高血压病的防治有重要的临床应用价值.     

高血压大鼠ACE2的表达及其与一氧化氮相关性分析

目的探讨血管紧张素转换酶2(ACE2)在自发性高血压大鼠(SHR)中的表达情况并对其与血清一氧化氮(NO)水平作相关性分析。方法分别采用实时荧光定量PCR,Northern印迹以及免疫印迹技术测定心、肾组织中ACE2的mRNA与蛋白表达情况,同时用硝酸还原酶法检测血清NO含量。结果与WKY对照组相比,SHR大鼠心、肾组织中ACE2的mRNA和蛋白表达均明显下降(ACE2/GAPDH mRNA拷贝数比值为:心脏0·043±0·012vs1.291±0·619;肾脏0·051±0·016vs0·914±0·433,P均<0·01;蛋白相对OD值为:心脏0·729±0·046vs1±0·053;肾脏0·734±0·063vs1.005±0·05,P均<0·01),同时出现血清NO浓度下降[(24.3±8.0vs78.4±27.9)μmol/L,P<0·01)。相关分析发现,大鼠血清NO水平与心、肾组织中ACE2/GAPDH的mRNA拷贝数比值呈正相关(r=0·610,0·521,P均<0·05),而与血压水平则呈负相关(r=-0·656,P<0·05)。结论SHR大鼠心、肾组织中ACE2的mRNA和蛋白表达均明显下降,很可能与体内NO水平降低及血压上升有关。特异性影响ACE2转录和表达的药物将对高血压病的防治有重要的临床应用价值。     

替米沙坦对自发性高血压大鼠心肌ACE2表达的影响

选择16只12周龄雄性自发性高血压大鼠随机分为自发性高血压组（SHR组,n=8）和替米沙坦组（n=8）,替米沙坦组大鼠予以替米沙坦5mg／（kg·d）灌胃,给药时间8周,同时取8只12周龄雄性Wistar大鼠作为对照组,利用免疫组织化学染色和逆转录聚合酶链反应检测各组动物心肌血管紧张素转换酶2（ACE2）的表达。结果发现,与对照组比较,SHR组心肌ACE2表达显著降低（P〈0．05）,与SHR组比较,替米沙坦组经8周治疗后,ACE2表达显著增高（P〈0．05）,替米沙坦组血压、心肌重量指数及心肌胶原容积分数较SHR组均明显下降（P均〈0．05）。认为高血压大鼠心肌ACE2表达降低,替米沙坦能够上调高血压大鼠心肌ACE2的表达,该作用可能为血管紧张素Ⅱ1型受体拮抗剂在高血压病心脏保护作用的新机制。     

缬沙坦对心肌病大鼠肾脏及心肌中ACE2 mRNA、ACE mRNA表达的影响

目的：探讨阿霉素诱导的心肌病大鼠肾脏及心肌组织中血管紧张素转换酶2(ACE2)mRNA、血管紧张素转换酶(ACE)mRNA的表达及缬沙坦对其的影响。方法：30只Wistar大鼠随机分为3组：正常对照组即生理盐水组(n=10)；生理盐水 阿霉素组(n=10)；阿霉素 缬沙坦组(n=10)。RT-PCR法检测肾、心肌组织中ACE2 mRNA、ACE mRNA的表达,光镜及透射电镜观察心肌病理变化。结果：阿霉素组大鼠较正常对照组大鼠肾脏及心肌组织中ACE2 mRNA(3．35±0．39对2．21±0．18,P=0．000；2．50±0．29对1．25±0．13,P=0．000)、ACE mRNA (2．31±0．38对1．19±0．12,P=0．000；1．77±0．09对0．84±0．11,P=0．000)的表达均明显增高,缬沙坦治疗组大鼠肾脏及心肌组织中ACE2 mRNA(2．65±0．34对3．35±0．39,P=0．001；1．72±0．32对2．50±0．29,P=0．000)、ACE mRNA (1．68±0．15对2．31±0．38,P=0．004；1．21±0．10对1．77±0．09,P=0．000)的表达较阿霉素组明显降低。结论：阿霉素诱导的心肌病大鼠肾脏及心肌组织中ACE2 mRNA、ACE mRNA表达水平均显著高于正常大鼠；缬沙坦对于阿霉素诱导的心肌病大鼠肾脏及心肌具有保护作用。     

当归挥发油对自发性高血压大鼠ACE2基因表达的影响

目的探讨当归挥发油对自发性高血压大鼠(SHR)心肌血肌紧张素转换酶(ACE)2基因表达的影响及作用机制。方法将40只8周龄雄性SHR随机分为模型组,当归挥发油组(低、高)和卡托普利组,并以同周龄的Wistar大鼠作为正常对照组。分别灌胃4 w后,取大鼠心肌组织,HE染色观察心肌组织形态学的变化实时荧光定量PCR法检测ACE2 mRNA表达量,Western印迹检测ACE2蛋白的表达水平。结果当归可降低SHR血压;HE染色显示,与模型组相比较,当归挥发油各组病变分别有不同程度的减轻;与模型组相比,当归高、低剂量组ACE2 mRNA及蛋白表达水平均明显升高(P<0.01)。结论当归挥发油对SHR血压有调节作用,可能通过ACE2基因发挥降压作用。     

缬沙坦对心肌病大鼠肾脏及心肌中ACE2 mRNA、ACE mRNA表达的影响

目的:探讨阿霉素诱导的心肌病大鼠肾脏及心肌组织中血管紧张素转换酶2(ACE2)mRNA、血管紧张素转换酶(ACE)mRNA的表达及缬沙坦对其的影响.方法:30只Wistar大鼠随机分为3组:正常对照组即生理盐水组(n=10);生理盐水 阿霉素组(n=10);阿霉素 缬沙坦组(n=10).RT-PCR法检测肾、心肌组织中ACE2 mRNA、ACE mRNA的表达,光镜及透射电镜观察心肌病理变化. 结果:阿霉素组大鼠较正常对照组大鼠肾脏及心肌组织中ACE2 mRNA(3.35±0.39对2.21±0.18,P=0.000;2.50±0.29对1.25±0.13,P=0.000)、ACE mRNA(2.31±0.38对1.19±0.12,P=0.000;1.77±0.09对0.84±0.11,P=0.000)的表达均明显增高,缬沙坦治疗组大鼠肾脏及心肌组织中ACE2 mRNA(2.65±0.34对3.35±0.39,P=0.001;1.72±0.32对2.50±0.29,P=0.000)、ACE mRNA(1.68±0.1 5对2.31±0.38,P=0.004;1.21±0.10对1.77±0.09,P=0.000)的表达较阿霉素组明显降低. 结论:阿霉素诱导的心肌病大鼠肾脏及心肌组织中ACE2mRNA、ACE mRNA表达水平均显著高于正常大鼠;缬沙坦对于阿霉素诱导的心肌病大鼠肾脏及心肌具有保护作用.     

N-domain angiotensin-converting enzyme isoform expression in tissues of Wistar and spontaneously hypertensive rats

BACKGROUND: Angiotensin I-converting enzyme (ACE) is a protein containing two active sites, called N- and C-domains, according to their position in the protein. AIM: The aim of the present study was to verify whether the expression of the N-domain ACEs detected in the urine of Wistar and spontaneously hypertensive (SHR) rats was restricted to the kidney. METHODS: Adrenal, aorta, heart, liver, lung, kidney and testicle tissue from Wistar rats and spontaneously hypertensive rats were homogenized in assay buffer and analyzed by gel filtration, Western blotting and radio-immunoassay. RESULTS: Two peaks (at 136 and 69 kDa) with ACE activity upon ZPhe-His-Leu were separated by gel filtration from homogenate tissues of Wistar rats, in contrast with the tissue from hypertensive rats, which showed ACE forms of 96 and 69 kDa. The bands detected by Western blotting for all studied tissue from Wistar and spontaneously hypertensive rats showed a correspondence with the two peaks containing ACE activity detected in the polyacrylamide gel slices. Angiotensin II levels were increased in hypertensive rat tissue when compared with Wistar rat tissues. In addition, captopril 3 micromol/l inhibited the enzymic activity, where the Km was in the order of mmol/l and micromol/l using hippuryl-His-Leu and Abz-Ser-Asp-Lys(Dnp)Pro-OH as substrates, respectively. All tissues from Wistar rats presented ACE with 136 kDa, similar to somatic ACE, and N-domain ACE with 69 kDa. In the same tissue of spontaneously hypertensive rats, 96 and 69 kDa N-domain ACEs were detected. CONCLUSIONS: Our results demonstrated that N-domain ACEs were not exclusively produced in the kidney and excreted in the urine; they were expressed in all tissue studied, suggesting that these enzymes could influence local angiotensin II production, contributing to organ-specific regulation.     

Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats

There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.     

Favorable cardiac and aortic remodeling in olmesartan-treated spontaneously hypertensive rats

Cardiovascular remodeling contributes to the progression of cardiovascular disease. Thus, our aim was to evaluate the action of long-term treatment with olmesartan on cardiac and aortic adverse remodeling and its relationship with blood pressure (BP) and tensile forces acting on the aortic wall. Five-month-old male rats were divided in: WKY group (n = 6), SHR group (n = 6), and SHRs treated with hydralazine 30 mg/kg/day (SHR-H, n = 8) or olmesartan 10 mg/kg/day (SHR-O, n = 8). Medications were administered for 16 weeks. The SHR group showed hypertension (189 ± 4 mmHg), cardiomyocyte hypertrophy (+107%), interstitial fibrosis (5.7% vs 1.9% in WKY), and reduced intramyocardial vascularization (9.1% vs 22.8% in WKY). In aorta, the SHRs showed outward hypertrophic remodeling, increased elastic fibers content (+36%), and increased circumferential wall tension (CWT, 2.79 × 10⁴ dyne/cm) and tensile stress (TS, 261.4 × 10⁴ dyne/cm²). Hydralazine and olmesartan decreased BP (−45% approximately) and likewise CWT and TS (−45% and −35% approximately). Both medications prevented left ventricle remodeling, but olmesartan improved cardiomyocyte hypertrophy better than hydralazine. Hydralazine did not alter media hypertrophy, but it enlarged lumen diameter and increased elastic fibers. It is unlikely that olmesartan prevented all aortic alterations. Taken together, long-term control of BP alone is not sufficient to prevent aortic remodeling due to hypertension, but in myocardium it seems to be enough, except for cardiomyocyte hypertrophy. The differential action of olmesartan suggests that it is essential to block growth stimulation by angiotensin II in cardiomyocytes and vascular smooth muscle cells in order to better prevent cardiovascular adverse remodeling due to arterial hypertension.     

RNA干扰血管紧张素转换酶对自发性高血压大鼠血压及心肌重构的影响

目的 用RNA干扰技术下调血管紧张素转换酶(ACE)表达,观察其对自发性高血压大鼠血压及心肌重构的影响.方法 自发性高血压大鼠随机分为3组,即空白对照组(尾静脉注射生理盐水),病毒对照组(尾静脉注射对照腺病毒),治疗组[尾静脉注射表达ACE基因特异性短发夹RNA(shRNA)的重组腺病毒载体],同时设WKY正常血压对照组.以上各组大鼠均于实验的第1、16天各注射1次.干预前后检测尾动脉压的变化.于首次注射后第3天,用RT-PCR及Western blot法检测心肌、主动脉组织中ACE mRNA及蛋白的表达,ELISA法检测血清中ACE的含量.实验结束时,检测左心重/体重及心肌胶原蛋白的含量,并用透射电镜观察心肌超微结构的变化.结果 治疗组于每次注射后,尾动脉压均明显下降22 mm Hg(1 mm Hg=0.133 kPa)左右,单次注射后降压作用至少可持续14 d,累积降压幅度达38 mm Hg左右,而空白对照和病毒对照组血压则持续升高.治疗组心肌、主动脉组织中ACE mRNA及蛋白表达明显低于空白对照组和病毒对照组(P＜0.05),而与WKY组比较差异无统计学意义.治疗组血清ACE含量(16.37±3.90)ng/ml也明显低于空白对照组(48.26±1.50)ng/ml和病毒对照组(46.67±2.82)ng/ml,P＜0.05,而与WKY组(14.88±3.15)ng/ml比较差异无统计学意义.治疗组左心重/体重与心肌胶原蛋白含量[2.24±0.19与(1.283±0.019)μg/mg]明显低于空白对照组[3.21±0.13与(1.686±0.013)μg/mg]和病毒对照组[3.13±0.12与(1.682±0.009)μg/mg],P均＜0.05,但还未降到WKY组水平[2.06±0.11与(1.257±0.019)μg/mg].电镜观察显示治疗组心肌超微结构得到了明显改善.结论 RNA干扰可有效下调ACE表达,降低自发性高血压大鼠血压,改善心肌重构.RNA干扰有望成为高血压病基因治疗的新方法.     

伊贝沙坦对自发性高血压大鼠肾脏血管紧张素转换酶2基因表达的影响

目的观察自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)的表达,探讨伊贝沙坦对SHR肾脏ACE2 mRNA表达的调节作用。方法20只14周龄雄性SHR分为SHR组和伊贝沙坦组,各10只。伊贝沙坦组每只大鼠予以伊贝沙坦50 mg·kg-1·d-1灌胃,给药时间12周。同时取14周龄雄性京都种Wistar大鼠10只为对照组。SHR组和对照组给予等量蒸馏水灌胃12周。采用免疫组织化学和逆转录聚合酶链反应检测各组大鼠肾脏ACE2表达,利用放射免疫测定法检测各组大鼠血浆血管紧张素(Ang)Ⅱ浓度。结果与对照组比较,SHR组ACE2 mRNA表达显著减少(0．72±0．11对1．11±0．15);与SHR组比较,伊贝沙坦组经12周治疗后,ACE2 mRNA表达明显提高(1．03±0．13对0．72±0．11),均为P<0．05。SHR肾脏ACE2 mRNA表达与血浆AngⅡ浓度成正相关(r=0．83,P<0．05)。结论ACE2在高血压大鼠肾脏表达显著减少,可能是高血压病理生理变化之一。AngⅡ-1型受体阻滞剂伊贝沙坦上调SHR肾组织ACE2 mRNA表达,提示这可能是该药物反向调节过度激活的肾素-血管紧张素系统又一新途径。     

Non-corresponding effects of an angiotensin-converting enzyme inhibitor on cardiac and vascular hypertrophy in spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors (ACEIs) may have different effects on cardiac hypertrophy than on vascular hypertrophy. Arginine vasopressin (AVP) may promote cardiac hypertrophy. Our aims were (1) to simultaneously examine the chronic effects of ACEIs on hypertrophy of the heart and hypertrophy of the coronary and renal interlobular arteries, and (2) to clarify the relation between AVP concentration (AVPC) and cardiac hypertrophy. ACEI (delapril: 30 mg/kg/day) or vehicle (5% arabic gum) was administered in a preventive (4 to 28 weeks of age) or a therapeutic (12-24 weeks of age) protocol in spontaneously hypertensive rats. In both protocols, delapril produced a slight but significant decrease in systolic blood pressure. In the therapeutic protocol, the weight of the left ventricle (mean+/-SE) was lower (p<0.05) in the ACEI group (64+/-2 mg/100 g body weight) than in the control group (69+/-1 mg/100 g body weight). Plasma renin activity was significantly higher in the ACEI group than in the control group in both the preventive (p <0.01) and therapeutic (p<0.01) protocols. In the therapeutic protocol, AVPC was significantly (p<0.05) lower in the ACEI group than in the control group. AVPC was significantly (p=0.02, r=0.46) correlated with the weight of the left ventricle in the therapeutic protocol. For both protocols, no differences were noted between the ACEI and control groups in the vascular hypertrophy of the coronary and renal interlobular arteries. We conclude that (1) the preventive or therapeutic effect of ACEIs on hypertrophy may not be the same in the heart as in the coronary and renal arteries; and (2) AVP was significantly correlated with the left ventricular weight. This indicates that AVP could play a role in the etiology of cardiac hypertrophy in SHR.     

Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats

Background

Farnesyltransferase (FT), an essential enzyme at the downstream of mevalonate pathway, was reported to be upregulated in hypertrophic cardiomyocytes of spontaneously hypertensive rats (SHRs) compared with myocardium of Wistar-Kyoto rats (WKYs). This upregulation was accompanied with cardiac remodeling. This study was designed to determine whether FT inhibition can alter cardiac remodeling in SHRs.

Methods

Twelve-week-old SHRs were randomized to receive infusion of either NS or FTI-276 (307 μg/kg/d i.v. each n = 10). WKY rats served as normal controls (n = 6). Echocardiography was performed before and after intervention. SHR hearts were perfused ex vivo for the evaluation of cardiac performance, collagen deposition and biochemical changes (activation of Ras, extracellular-signal regulated kinases/ERK1/2, procollagen type ?/Ш, TGF-β1, connective tissue growth factor/CTGF, and bone morphogenetic protein-7/BMP-7 expression).

Results

FTI-276 intervention decreased interventricular septum wall thickness at end- diastole (IVSd) and relative wall thickness (RWT) of SHRs (P< 0.05). Three week intervention with FTI-276 attenuated hydroxyproline content (P < 0.05), collagen deposition (P < 0.01), Ras activation, ERK1/2 phosphorylation (P < 0.01) and mRNA expression of procollagen type I, TGF-β1 and CTGF and elevated mRNA expression of BMP-7 (P < 0.05) in left ventricle of SHRs.

Conclusion

The present study indicated that FT inhibition could attenuate myocardial fibrosis and partly improve cardiac remodeling in SHRs. The beneficial effects might be mediated through suppression of the activation of Ras and ERK1/2 phosphorylation pathway. The enhanced mRNA expression of BMP-7 with inhibition of TGF-β1 and CTGF mRNA expression might be an important mechanism.