不同降压药物对自发性高血压大鼠模型左室心肌细胞中TRPC3及TRPC6表达的影响

目的探讨缬沙坦、雷米普利及氨氯地平对自发性高血压大鼠(SHR)左室心肌中瞬时受体通道蛋白C亚族3及6(TRPC3及TRPC6)表达的影响。方法将24只12周龄SHR大鼠随机分为4组,即SHR组、缬沙坦组、雷米普利组及氨氯地平组,每组6只。另以6只同龄的Wistar Kyoto大鼠(WKY)为正常对照组。给药4周后,检测各组大鼠的血压、左室质量指数、左室心肌细胞横径;RTPCR及Western Blot检测TRPC3及TRPC6 mRNA及其蛋白的表达。结果 SHR组血压、左室质量指数及左室心肌细胞横径均明显高于对照组(P<0.05),3个药物组上述指标均较SHR组降低。结论 SHR组及对照组大鼠均有TRPC3及TRPC6的表达,TRPC3及TRPC6可能共同参与调节心肌肥厚的病理生理过程;缬沙坦可能通过抑制TRPC3蛋白的表达参与逆转左室肥厚的过程。     

不同降压药物对自发性高血压大鼠模型左室心肌细胞中TRPC3及TRPC6表达的影响

目的探讨缬沙坦、雷米普利及氨氯地平对自发性高血压大鼠(SHR)左室心肌中瞬时受体通道蛋白C亚族3及6(TRPC3及TRPC6)表达的影响。方法将24只12周龄SHR大鼠随机分为4组,即SHR组、缬沙坦组、雷米普利组及氨氯地平组,每组6只。另以6只同龄的Wistar Kyoto大鼠(WKY)为正常对照组。给药4周后,检测各组大鼠的血压、左室质量指数、左室心肌细胞横径;RTPCR及Western Blot检测TRPC3及TRPC6 mRNA及其蛋白的表达。结果 SHR组血压、左室质量指数及左室心肌细胞横径均明显高于对照组(P<0.05),3个药物组上述指标均较SHR组降低。结论 SHR组及对照组大鼠均有TRPC3及TRPC6的表达,TRPC3及TRPC6可能共同参与调节心肌肥厚的病理生理过程;缬沙坦可能通过抑制TRPC3蛋白的表达参与逆转左室肥厚的过程。     

不同降压药物干预对自发性高血压大鼠主动脉瞬时受体电位通道C亚族表达的影响

目的:研究雷米普利、缬沙坦和氨氯地平对自发性高血压大鼠(SHR)主动脉(内膜及平滑肌)的瞬时受体电位通道C亚族3亚型及6亚型(TRPC3、TRPC6)表达的影响.方法:24只SHR随机分成4个组(η=6),1个SHR对照组,雷米普利组、缬沙坦组和氨氯地平组,采用灌胃法给药4周,另用6只Wistar鼠(WKY)作正常WKY组,观察给药治疗4周前后血压变化,实验结束时取主动脉组织进行TRPC3和TRPC6的检测,采用逆转录多聚酶链反应(RT-PCR)法检测信使核糖核酸(mRNA)的表达,免疫组织化学法及蛋白免疫印迹(Western Blot)法检测蛋白的表达.结果:SHR对照组与正常WKY组治疗前比较,血压明显增高(P<0.05),SHR对照组与正常WKY组治疗后比TR-PC3、TRPC6的mRNA和蛋白表达显著增加(P均<0.05),差异均有统计学意义.药物治疗4周后,雷米普利组、缬沙坦组、氨氯地平组与治疗前比血压均有效地降低(P均<0.05),TRPC3的mRNA和蛋白表达均减少(P均<0:05),差异均有统计学意义.TRPC6的mRNA和蛋白表达改变不明显,雷米普利组、缬沙坦组、氨氯地平组间TRPC3、TRPC6的mRNA和蛋白表达差异无统计学意义.结论:SHR大鼠主动脉TRPC3及TRPC6的mRNA和蛋白表达明显增高,给予雷米普利、缬沙坦和氨氯地平4周后血压下降,同时TRPC3mRNA和蛋白表达降低,提示TRPC3可能参与了SHR大鼠血压调控.     

雷米普利通过干预瞬时感受器阳离子通道C3的表达对心肌纤维化的影响

目的研究雷米普利对自发性高血压大鼠心肌纤维化时心脏瞬时感受器阳离子通道C3亚族表达的影响。方法 12周龄SHR大鼠随机分为安慰剂组、雷米普利组,同龄Wistar Kyoto rats(WKY)为正常对照组,雷米普利给药4周后测左室质量指数、心肌胶原容积分数和心脏组织中TRPC3通道的mRNA的表达和蛋白的表达。结果安慰剂组左室质量指数,Ⅰ、Ⅲ型胶原容积分数显著高于WKY组;雷米普利组上述指标较安慰剂组明显降低。3组心脏均有TRPC3的表达,但安慰剂组TRPC3 mRNA及蛋白表达显著高于WKY组,雷米普利组TRPC3表达则明显少于SHR组(P<0.05)。结论 SHR及WKY大鼠存在TRPC3蛋白的表达,心脏TRPC3蛋白可能参与了心肌纤维化发生发展的过程,雷米普利可能通过下调心脏TRPC3mRNA及蛋白的表达发挥抗心肌纤维化的作用。     

依那普利和缬沙坦对自发性高血压大鼠心肌细胞凋亡的影响

目的观察依那普利和缬沙坦在降压的同时对自发性高血压大鼠(SHR)左室肥厚过程中心肌细胞凋亡及凋亡相关蛋白bc l-2、bax表达的影响。方法14周龄雄性SHR随机分为三组(n=6),依那普利组:依那普利30 mg.kg-1.d-1;缬沙坦组:缬沙坦30 mg.kg-1.d-1;对照组:等量饮用水灌胃,干预8周。分别采用流式细胞术Annexin V/PI法和免疫组化SABC法检测心肌细胞凋亡指数及凋亡相关蛋白bc l-2、bax的表达。结果缬沙坦及依那普利治疗组大鼠血压及左室重量/体重明显降低,心肌细胞凋亡指数明显降低(P<0.01);依那普利组明显降低bax蛋白表达,增加bc l-2蛋白表达(P<0.01)。缬沙坦组明显降低bax蛋白表达(P<0.01)。结论依那普利和缬沙坦对SHR左室肥厚过程中心肌细胞凋亡均有抑制作用。两者均通过增加bc l-2/bax比率而抑制心肌细胞凋亡,逆转高血压引起的左室肥厚。     

自发性高血压大鼠肥厚左室心肌组织微小RNA-1与内向整流钾通道2.1表达的改变及其意义

目的观察自发性高血压大鼠(SHR)肥厚的左室心肌组织微小RNA-1、内向整流钾通道2.1(Kir2.1)表达的变化及其关系,以探讨高血压左心室肥厚(LVH)发生室性心律失常的分子机制。方法取10只17周龄雄性SHR为LVH组,10只8周龄雄性SHR为阳性对照组,10只17周龄雄性WKY大鼠作为空白对照组,通过HE染色、心肌细胞横径测量、实时荧光定量聚合酶链反应(qRT-PCR)、免疫组织化学法及Western blot检测等方法,检测大鼠左室心肌组织病理学改变、微小RNA-1表达、Kir2.1蛋白表达水平的改变。结果①与空白对照组比较,LVH组和阳性对照组的收缩压、舒张压明显升高(分别P<0.01,P<0.05);②与两对照组相比,LVH组的左室质量指数及心肌细胞横径均明显增大(均P<0.05),左室心肌细胞明显肥大,心肌间质增多,伴随着微小RNA-1表达水平明显升高,Kir2.1蛋白表达水平显著降低(P<0.05);③LVH组大鼠左室心肌组织微小RNA-1与Kir2.1蛋白的表达水平呈负相关(r=-0.720,P<0.05)。结论SHR肥厚左室心肌组织微小RNA-1表达上调,并伴随Kir2.1表达下调。     

自发性高血压大鼠肥厚左室心肌组织微小RNA-1与缝隙连接蛋白43的改变

目的观察自发性高血压大鼠(SHR)肥厚左室心肌组织微小RNA-1(miRNA-1)、缝隙连接蛋白43(Cx43)表达的变化及其关系,以探讨高血压性心肌肥厚发生室性心律失常(VA)的分子机制。方法 10只17周龄雄性SHR大鼠做为左室肥厚组(LVH组),10只8周龄雄性SHR大鼠做为对照组,通过病理学、心肌细胞横径的测量、实时荧光定量聚合酶链反应、免疫组织化学法及western blotting检测等方法 ,比较两组大鼠左室心肌组织病理学改变、miRNA-1及Cx43蛋白表达。结果①与对照组比较,LVH组的收缩压、舒张压升高,左室质量指数及心肌细胞横径均明显增大(P均0.05);miRNA-1表达水平明显升高,以及Cx43蛋白表达水平降低(0.27±0.10vs0.60±0.13,P0.05);②LVH组大鼠左室心肌组织miRNA-1与Cx43蛋白的表达水平呈显著负相关(r=-0.661,P0.05)。结论 miRNA-1可能通过抑制Cx43表达而参与高血压LVH发生VA。     

左旋氨氯地平对自发性高血压大鼠左室肥厚及内皮素-1表达的影响

目的 观察左旋氨氯地平对自发性高血压大鼠(SHR)左室肥厚的影响,并探讨其对内皮素(ET-1)的作用.方法 20只SHR随机分为左旋氨氯地平治疗组和高血压对照组,同周龄的WKY大鼠作为正常对照组.给药12周,测量左室肥厚指标的变化,采用心室导管法检测心功能的变化,放免法测定左心室心肌ET-1含量,实时定量PCR法测定左心室心肌中前内皮素原(preproET-1) mRNA 的表达.结果 与高血压对照组相比左旋氨氯地平干预能够改善SHR左室收缩和舒张功能参数(+dp/dtmax/LVSP、-dp/dtmax/LVSP)(P<0.05),降低左室质量指数(P<0.01);左旋氨氯地平干预能够降低SHR心肌 ET-1含量(P<0.05),使心肌preproET-1 mRNA的表达降低约20%(P<0.05).结论 左旋氨氯地平能够抑制SHR的左室肥厚,并改善左室收缩和舒张功能,其作用机制可能与调节心肌ET-1的水平有关.     

缬沙坦与硝苯地平对自发性高血压大鼠左心室肥厚心肌细胞G 蛋白偶联受体激酶2的表达及亚细胞分布的影响

目的 观察缬沙坦及硝苯地平对自发性高血压大鼠(SHR)左心室肥厚心肌细胞G 蛋白偶联受体激酶2(GRK2)的表达及亚细胞分布的影响.方法 选择自发性高血压大鼠(SHR)为研究对象(n=30),随机分为对照组(n=6),低剂量缬沙坦组[L 缬沙坦,10 mg /(kg·d),n=6],高剂量缬沙坦组[H缬沙坦,30 mg /(kg·d),n=6],低剂量硝苯地平组[L 硝苯地平,10 mg /kg,2 次/ d,n=6],高剂量硝苯地平组[H 硝苯地平,30mg /(kg·次),2 次/d,n=6],由6 月龄喂养至8月龄,处死后分离心脏,通过免疫荧光标记、激光共聚焦显微镜及Werstern Blot 等方法,观察左心室心肌细胞GRK2的表达及亚细胞分布的变化.结果 与对照组比较,两药物干预的SHR 左心室心肌细胞膜蛋白GRK2表达及分布减少,高剂量较低剂量又有进一步减少,差异均有统计学意义(均P＜0.05).缬沙坦组左心室心肌细胞膜蛋白GRK2表达及左心室重量较硝苯地平组减少,差异有统计学意义(P＜0.05).相关性分析结果示两药物干预组大鼠左心室心肌细胞膜蛋白GRK2透光密度与左心室重量呈正相关(缬沙坦组r＝0.837,硝苯地平组r＝0.829,均P＜0.01).结论 缬沙坦与硝苯地平改善左心室肥厚可能与抑制SHR 左心室心肌细胞膜蛋白GRK2表达有关,缬沙坦较硝苯地平能更好地改善心肌肥厚可能与其抑制GRK2表达使其进一步减少有关.     

慢性低氧及野百合碱对SD大鼠右心室功能及规范性瞬时感受器电位亚家族表达的影响

目的探讨慢性低氧(CH)及野百合碱(MCT)对SD大鼠右心室功能及右心室心肌细胞上规范性瞬时感受器电位(TRPC)亚家族表达的变化。方法将72只SD雄性大鼠随机平均分为对照组(CON组)、CH组和MCT诱导右心室肥大模型组(MCT组),每组24只。CH组将大鼠置于CH(10%O2)环境饲养3 w以诱导大鼠发生右心室肥厚,MCT组则是对SD大鼠进行腹腔注射诱导液,其剂量规定是2%MCT 60 mg/kg,设计MCT诱导大鼠出现右心室肥厚模型。之后对上述三组SD大鼠的右心室进行全面检查,研究其血流动力学指标和右心肥大指数(RVMI)、右心室心肌病理切片,实时定量PCR法和免疫印迹法检测TRPC亚家族m RNA和相关蛋白的表达水平。结果与CON组比较,CH组及MCT组:SD大鼠的右心室功能相关指标收缩压(RVSP)、右心室内压力最大上升速率(+dp/dtmax)、RVMI均显著增加(P<0.01),且MCT组的血流动力学改变及RVMI均显著高于CH组;心肌纤维组织呈病态状,纤维层变厚,胞核颜色加重、外形不规则,同时经检测发现,MCT组的病理改变较CH组更为显著;CH组右心室心肌组织TRPC1 m RNA表达升高;MCT组右心室心肌组织TRPC6 m RNA表达升高;CH组大鼠右心室TRPC1蛋白指数异常,其表达率增加,MCT组大鼠右心室TRPC6蛋白指数异常,其表达率增加(P<0.05)。结论在CH环境中生长3 w能够顺利诱导大鼠出现右心室肥厚,同时也会提高其心肌细胞中的TRPC1 m RNA与蛋白的表达,MCT预处理3 w可成功诱导SD大鼠产生右心室心肌肥厚,且MCT预处理的诱导的右心室肥厚现象比较明显,同时也提高其心肌细胞中的TRPC6 m RNA与蛋白的表达,这两个亚型或许是诱导右心室肥厚出现的重要因素。     

Increased transient receptor potential channel TRPC3 expression in spontaneously hypertensive rats

BACKGROUND: Disturbances in the regulation of cytosolic calcium concentration have been attributed to primary hypertension, but the role of calcium-permeable transient receptor potential canonical channel 3 (TRPC3) has not yet been evaluated in primary hypertension. METHODS: Expression of TRPC3 was determined using in-cell Western assay. Evaluation of RNA interference for the downregulation of a specific gene in cells by small interfering RNA was performed. Measurements of cytosolic calcium were carried out using the fluorescent dye fura2. RESULTS: Expression of TRPC3 was significantly increased in monocytes from spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Transplasmamembrane calcium influx and thapsigargin-induced sustained calcium increase were significantly higher in SHR compared with WKY. In the presence of the TRP channel blocker SKF-96365 these differences were no longer observed. Specific TRPC3-knockdown by transfection of monocytes from SHR with small interfering RNA significantly reduced TRPC3 expression, trans-plasma membrane calcium influx, and thapsigargin-induced sustained calcium increase. CONCLUSIONS: This study shows, for the first time, increased TRPC3 channel expression and increased TRPC3-related calcium influx in SHR.     

TRPC1, CaN and NFATC3 signaling pathway in the pathogenesis and progression of left ventricular hypertrophy in spontaneously hypertensive rats

Abstract

Spontaneously hypertensive rats (SHR) was used to study left ventricular hypertrophy (LVH) and its dynamic change after the interventions with Telmisartan and Amlodipine. The results showed that the expression of TRPC1, CaN and NFATC3 increased gradually with the pathogenesis and progression of LVH. Telmisartan reduced blood pressure and LVH, and down-regulated the expression of TRPC1, CaN and NFATC3 in left ventricle of SHR. Amlodipine reduced the blood pressure in SHR but had no impact on the hypertrophy and expression of above factors. Our data suggest that the pathogenesis and progression of LVH in SHR are related to upregulation of TRPC1, CaN and NFATC3 signaling pathway.     

Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats

Recent evidence suggests that elevated plasma levels of Trimethylamine-N-oxide (TMAO) can prolong the duration of elevated blood pressure in rats. The purpose of this study was to investigate the plasma TMAO level in Spontaneously Hypertensive Rats (SHR) and to explore the possible relationship between TMAO and aquaporin-2 (AQP-2) in the formation of hypertension. Twelve-week-old, male Spontaneously Hypertensive rats (SHR, n = 40) and Wistar-Kyoto rats (WKY, n = 40) were accordingly grouped into SHR group and WKY group. Each group was divided randomly into four subgroups: Untreated group, TMAO group, TMAO+Tolvaptan (TMAO+TVP) group, and TVP group, respectively. Systolic blood pressure (SBP), plasma TMAO, plasma osmolality (POsm), plasma vasopressin (PAVP), and plasma AQP-2 (PAQP-2) concentration were measured, and the expression of AQP-2 in kidney medulla was detected by RT-PCR and Western blot. At 14 weeks, rats in SHR TMAO group were shown the increased plasma TMAO, POsm, PAVP, and PAQP-2 levels, while those rats in SHR TMAO+TVP group were shown the decreased plasma TMAO, POsm, and PAQP-2 levels, but an even higher PAVP (due to the blockage of TVP to V2 receptor). These findings indicate that an increase of plasma TMAO levels in SHR leads to a higher plasma osmotic pressure, triggers the regulation of the TMAO-AVP-AQP-2 axis in SHR, elicits the greater water reabsorption, and eventually leads to hypertension.     

TRPC1对慢性阻塞性肺疾病慢性气道炎症的影响

目的探讨瞬时感受器电位通道C1(TRPC1)在慢性阻塞性肺疾病(慢阻肺)患者支气管黏膜上皮的表达水平及其与慢性气道炎症之间的关系。方法选取因不明原因肺部结节行纤维支气管镜检查的78例患者,依据慢性阻塞性肺疾病诊治指南分为慢阻肺组(46例)及对照组(32例),其中慢阻肺组再随机分为两个亚组:每日3次规律使用吸入型激素(ICS)布地奈德(ICS组,23例)及安慰剂(非ICS组,23例)治疗。所有受检查者均行支气管肺泡灌洗及支气管镜下刷检。Western Blot及qRT-PCR法检测刷检支气管上皮细胞内TRPC1表达水平,支气管肺泡灌洗液(BALF)行细胞学分类计数。酶联免疫吸附法检测BALF上清液中炎症介质白细胞介素13(IL-13)、成纤维生长因子2(FGF-2)表达水平。结果慢阻肺组支气管上皮细胞内的TRPC1 mRNA、蛋白表达水平明显高于对照组(P<0.05);ICS组的TRPC1表达水平低于非ICS组(P<0.05)。与对照组相比,慢阻肺组BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平均明显升高(P<0.05)。而ICS组BALF中的中性粒细胞、巨噬细胞、嗜酸性粒细胞、淋巴细胞计数及IL-13、FGF-2表达水平则低于非ICS组(P<0.05)。相关性分析结果显示,TRPC1 mRNA和蛋白表达水平与肺功能第一秒用力呼吸容积(FEV 1)占预计值百分比(FEV 1/Pre%)呈负相关(P<0.01),而与BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平呈正相关(P<0.05)。结论TRPC1可能通过参与慢阻肺慢性气道炎症过程促进疾病的发生发展,而ICS在一定程度上可干预该作用。     

全反式维甲酸对高血压大鼠心脏氧化应激水平的影响

目的:探讨全反式维甲酸(atRA)对高血压心脏还原型辅酶I氧化酶P22亚单位(p22phox)表达以及氧化应激水平的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射at-RA,为期1月。分别采用免疫印迹、硫代巴比妥酸比色以及透射电镜技术测定atRA治疗后SHR心脏p22phox的表达、丙二醛(MDA)含量以及心肌超微结构情况。结果:与WKY对照组相比,SHR心脏组织中p22phox蛋白表达与MDA含量明显升高(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中p22phox蛋白表达与MDA水平出现下调(P均<0.05),同时伴有心肌损伤减轻。结论:长期atRA治疗可降低SHR大鼠心脏组织中p22phox表达与MDA水平,提示atRA在高血压病中具有一定的抗氧化效应。     

Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins

Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isoforms of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2, 5, 8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166 +/- 11 to 89 +/- 5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53 +/- 0.14 to 1.96 +/- 0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3 decreased in SHR substantially from 35 +/- 3% to 13 +/- 1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3 myosin expression in the SHR during regression (r = 0.697, p less than 0.001). However, only the adult isoforms of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of chronic oral treatment with imidapril and TCV-116 on the responsiveness to angiotensin II in ventrolateral medulla of SHR.

OBJECTIVE: To examine whether chronic oral treatment with an angiotensin-converting enzyme inhibitor imidapril and an angiotensin II type 1 receptor antagonist TCV-116 would alter the response to angiotensin II in the rostral ventrolateral medulla. METHODS: Twelve-week-old spontaneously hypertensive rats (SHR) were treated with imidapril (20 mg/kg per day, n = 7), TCV-116 (5 mg/kg per day, n = 8) or vehicle (n = 8) for 4 weeks. Wistar- Kyoto rats (WKY) (n = 8) served as normotensive controls. At 16 weeks of age, angiotensin II (100 pmol) was microinjected into the rostral ventrolateral medulla of anaesthetized rats. RESULTS: Blood pressure decreased significantly in the rats treated with either imidapril or TCV-116. Pressor responses to angiotensin II microinjected into the rostral ventrolateral medulla were comparable in the untreated SHR, the imidapril-treated SHR and WKY (12 +/- 2, 15 +/- 4 and 10 +/- 1 mmHg, respectively), but were abolished in SHR treated with TCV-116 (0 +/- 2 mmHg, P< 0.01). Angiotensin-converting enzyme activity in the brain stem was significantly lower in SHR treated with imidapril (0.70 +/- 0.06 nmol/mg per h), but significantly higher in SHR treated with TCV-116 (1.62 +/- 0.04 nmol/mg per h) than in the untreated SHR (1.37 +/- 0.05 nmol/mg per h). CONCLUSIONS: Chronic oral treatment with imidapril and TCV-116 may have divergent influences on the renin-angiotensin system within the brain stem. TCV-116, but not imidapril, abolishes the pressor effect of angiotensin II in the rostral ventrolateral medulla.     

Upregulation of TRPC1 in the development of cardiac hypertrophy

The importance of Ca(2+) entry in the cardiac hypertrophic response is well documented, but the actual Ca(2+) entry channels remain unknown. Transient receptor potential (TRP) proteins are thought to form either homo- or heteromeric Ca(2+) entry channels that are involved in the proliferation and differentiation of various cells. The purpose of this study was to explore the potential involvement of TRP channels in the development of cardiac hypertrophy. The mRNA and protein expression of several TRP channel subunits were evaluated using hearts from abdominal aortic-banded (AAB) rats. Although TRPs C1, C3, C5, and C6 were constitutively expressed, only TRPC1 expression was significantly increased in the hearts of AAB rats compared to sham-operated rats. Using primary cultures of neonatal rat cardiomyocytes, we detected increases in the expression of TRPC1, brain natriuretic peptide (BNP), and atrial natriuretic factor (ANF), as well as increases in store-operated Ca(2+) entry (SOCE) and cell surface area, following endothelin-1 (ET-1) treatment. Silencing of the TRPC1 gene via small interfering RNA (siRNA) attenuated SOCE and prevented ET-1-, angiotensin-II (AT II)-, and phenylephrine (PE)-induced cardiac hypertrophy. In HEK 293T cells, overexpression of TRPC1 augmented SOCE, leading to an increase in nuclear factor of activated T cells (NFAT) promoter activity, while co-transfection with dominant-negative forms of TRPC1 suppressed it. In conclusion, TRPC1 functions in Ca(2+) influx, and its upregulation is involved in the development of cardiac hypertrophy; moreover, it plays an important role in the regulation of the signaling pathways that govern cardiac hypertrophy. These findings establish TRPC1 as a functionally important regulator of cardiac hypertrophy.