血管紧张素Ⅱ诱导下肥大心肌电生理特征和钙调神经磷酸酶活性的改变

目的:探讨血管紧张素Ⅱ(AngⅡ)诱导心肌肥大过程中心肌细胞电生理特性和钙调神经磷酸酶(CaN)活性的改变及其意义.方法:体外培养乳兔心室肌细胞,观察10-7mol/L Ang Ⅱ作用48h心肌细胞肥大指标(细胞体积、总蛋白含量及膜电容)、CaN活性、动作电位时程(APD)、瞬时外向钾电流(Ito)密度的变化.结果:AngⅡ作用48 h,心室肌细胞体积、总蛋白含量、膜电容较正常对照组分别增加40.36%、40.44%、38.22%(P＜0.01);心室肌细胞CaN活性较对照组增加114.7%(P＜0.01);心室肌细胞动作电位复极达90%时限(APD90)较对照组延长22.1%(P＜0.01);心室肌细胞Ito密度较对照组下调28.6%(P＜0.05).结论:AngⅡ持续刺激可引起心室肌细胞电重构,可能是导致室性心律失常发生的一个重要机制;CaN依赖的信号通路参与AngⅡ诱导的心肌肥大.     

不同类型大鼠左心室流出道诱发电位特征比较

目的观察不同类型高血压大鼠引起的心肌肥厚时,左心室流出道自发电活动及诱发电位特征.方法玻璃微电极细胞内记录方法,记录自发性高血压大鼠(SHR)和盐性高血压大鼠(SDsa)左心室流出道自发电活动,并从静息电位(RP)、动作电位幅值(APA)、0相最大除极速度(Vmax)、动作电位时程(APD)、复极至50%和90%时间(APD50和APD90)比较了其诱发电位的特征.结果 SHR其自发放电频率为88.9%,8例SDsa无一例引出自发电位.SHR诱发电位的APD、APD50和APD90延长,SDsa诱发电位的Vmax减慢,APD和APD 90缩短.结论不同类型高血压大鼠心肌肥厚时,左心室流出道自发放电频率不同,其诱发电位的特征也不相同.     

左室肥厚单个心肌细胞三层跨膜动作电位的不均一性改变

为探讨兔左室肥厚心肌内膜下、中层及外膜下单个细胞跨膜动作电位 (AP)的不均一性改变。将实验兔分为手术组和假手术组。手术组行腹主动脉缩窄术制备心肌肥厚模型 ,假手术组仅分离暴露腹主动脉而不缩窄。按胶元酶二步消化法分离兔心室肌细胞 ,其中用剃须刀分离左室游离壁内、中、外三层心肌。采用全细胞膜片钳记录AP。结果 :手术组三层心肌细胞AP复极达 90 %的时程 (APD90 ) (内膜下 :181± 18ms,中层 :2 4 6± 2 1ms,外膜下 :196± 15ms)较假手术组均明显延长 (内膜下 :14 2± 13ms,中层 :182± 15ms,外膜下 :15 8± 16ms,n =13,P <0 .0 1～ 0 .0 5 ) ,且以中层心肌细胞延长比例最大。手术组早期后除极的发生率明显大于假手术组 (6 0 %vs 10 % ,n =10 ,P <0 .0 0 1)。结论 :兔左室肥厚三层心肌细胞间的跨室壁复极不均一性明显增大。     

牛磺酸对甲亢豚鼠心室肌细胞电生理特性的影响

目的观察牛磺酸(Taurine T)对甲状腺机能亢进(以下简称甲亢)豚鼠离体心室肌细胞动作电位的影响,探讨牛磺酸对甲亢豚鼠心室肌细胞电活动的影响及其机制.方法采用微电极技术,引导心室肌细胞动作电位,观察在甲亢状态下牛磺酸对心室肌细胞动作电位各参数的影响.结果 (1)甲亢组豚鼠心室肌细胞动作电位时程(APD20, APD50, APD90, APD)及有效不应期(ERP)显著缩短,甲亢豚鼠心室肌细胞动作电位幅度(APA),零期最大除极速率(Vmax)无显著性变化;(2)加入牛磺酸后,甲亢豚鼠心室肌细胞动作电位时程APD50, APD90, APD显著延长,而APD20及动作电位幅度(APA)无显著变化 ,零期最大除极速率(Vmax)显著降低,ERP显著延长;(3)给甲状腺功能正常组加入牛磺酸后,豚鼠心室肌细胞动作电位时程APD20, APD50, APD90显著缩短,APD亦有缩短,但无显著性差别,ERP显著延长,APA无显著性变化,Vmax显著性降低.结论 (1)较高浓度的牛磺酸可能对甲亢豚鼠的离体心室肌细胞膜的外向(主要是K )电流具有一定的抑制作用;(2)对甲状腺功能正常豚鼠的心室肌细胞,一定程度上,可能促进钾外流;(3)无论是正常组还是甲亢组,在加入牛磺酸后,Vmax均出现显著降低,提示较高浓度的牛磺酸对心室肌细胞的INa也有影响.     

不同类型大鼠左心室流出道诱发电位特征比较

目的 观察不同类型高血压大鼠引起的心肌肥厚时，左心室流出道自发电活动及诱发电位特征。方法 玻璃微电极细胞内记录方法，记录自发性高血压大鼠(SHR)和盐性高血压大鼠(SDsa)左心室流出道自发电活动，并从静息电位(RP)、动作电位幅值(APA)、0相最大除极速度(Vmax)、动作电位时程(APD)、复极至50％和90％时间(APD50和APD90)比较了其诱发电位的特征。结果 SHR其自发放电频率为88．9％，8例SDsa无一例引出自发电位。SHR诱发电位的APD、nPD50和APD90延长，SDsa诱发电位的Vmax减慢，APD和APD90缩短。结论 不同类型高血压大鼠心肌肥厚时，左心室流出道自发放电频率不同，其诱发电位的特征也不相同。     

兔肥厚左心室跨壁复极离散度和室性心律失常发生机制

目的 探讨肥厚左心室跨壁复极离散度变化及室性心律失常发生机制.方法 制作压力超负荷兔模型,分别记录对照组、肥厚组心室肌内、外膜动作电位并同步记录跨室壁心电图,比较两组动作电位时限（APD90）、跨心室壁复极离散度（TDR）和室性心律失常发生率、尖端扭转性室性心动过速（Tdp）危险度评分.结果 （1）与对照组相比,肥厚组内、外膜APD90显著延长,以内膜层心肌更为明显;TDR显著增大（P＜0.01）;上述变化呈现显著慢频率依赖性;（2）肥厚组室性心律失常发生率、Tdp危险度评分明显高于对照组.结论 动作电位时限延长、跨心室壁复极离散度增大基础上的早期后除极和跨室壁折返激动是肥厚心室心律失常的主要机制.     

大豆异黄酮对豚鼠乳头肌动作电位和心肌细胞钠电流的影响

目的 观察大豆异黄酮(soybean isoflavone,SI)对豚鼠乳头肌动作电位的影响和培养心室肌细胞钠电流的作用.方法 采用悬浮玻璃微电极法测定乳头肌的动作电位和全细胞膜片钳方法测定心室肌细胞的钠电流.结果 SI能剂量依赖性地降低乳头肌动作电位幅值(APA),且能同时缩短复极50%及90%水平的动作电位时程(APD50、APD90);SI 0.1μg/ml和1.0μg/m1对心室肌细胞钠电流抑制率是14.39%和23.48%.结论 SI对心肌有负性肌力作用,可使心肌细胞动作电位除极参数降低,动作电位时程缩短,对钠电流的抑制是其负性肌力作用和抗心律失常作用的离子机制之一.     

异丙酚对家兔心室外膜心肌细胞动作电位和L-型钙电流的影响

目的研究异丙酚对家兔左、右心室心外膜心肌细胞动作电位和L-型钙电流的影响。方法酶解法分离家兔左、右心室心外膜心肌细胞。全细胞膜片钳技术记录左、右心室心外膜心肌细胞动作电位和L-型钙电流(ICa-L)在使用异丙酚前后的变化。结果在电流钳制下,左、右心室心外膜心肌细胞动作电位都具有从0期到4期的动作电位形态,2相平台期有心外膜心肌细胞特有的穹窿样突起。异丙酚使右室心外膜心肌细胞动作电位失去2相平台期穹窿样突起,呈三角形尖锥锋形。左、右心室心外膜心肌细胞动作电位时程复极化50%和90%(APD50和APD90)在异丙酚作用后都明显缩短,其中右室心外膜心肌细胞APD50和APD90缩短最为明显(P<0.05或0.01)。在电压钳制下,异丙酚使左、右心室心外膜心肌细胞ICa-L在同一指令电位下,电流幅度均明显减小,但右室心外膜心肌细胞ICa-L的减小幅度明显强于左室同层ICa-L的减小幅度(P<0.01)。异丙酚还使左、右心室心外膜心肌细胞ICa-L的I-V曲线上移,并且使右室心外膜心肌细胞ICa-L的I-V曲线处在所有I-V曲线最上部。结论异丙酚对右室心外膜心肌细胞动作电位和ICa-L的影响程度明显强于左室,从而引起左、右心外膜心肌细胞电不均一性。     

左心室肥厚跨室壁电不均一性及缬沙坦对其影响的实验研究

目的 :探讨肥厚心肌跨室壁复极不均一性及缬沙坦预防性给药的影响。方法 :家兔 30只 ,随机分为 3组 ,腹主动脉缩窄组 (缩窄组 )、假手术组、用药组。主动脉缩窄术制备家兔高血压心肌肥厚模型 ,胶原两步消化法分离获取左心室内膜、中层及外膜单个心肌细胞 ,以全细胞膜片钳技术记录单细胞跨膜动作电位和离子流。结果 :腹主动脉缩窄组外膜、中层、内膜 3层心肌细胞跨膜动作电位复极达 90 %时程 (APD90 )均较假手术组及用药组延长 ,有显著性差异 (P <0 0 5～ 0 0 1)。以中层心肌细胞延长最为明显 (延长比例 :中层 2 3% ,外膜 10 % ,内膜 8% ) ,使肥厚心肌跨室壁复极不均一性明显增大。用药组与假手术组间各层细胞跨膜动作电位复极达 90 %时程均无明显差异。缩窄组各层心肌细胞瞬时外向钾电流 (Ito)和延迟整流钾电流 (Iks)密度均较用药组及假手术组下降 ,有显著性差异 (P <0 0 5 ) ,以中层细胞下降的幅度最大 ,而用药组及假手术组间心肌细胞瞬时外向钾电流、延迟整流钾电流密度无显著差异。结论 :家兔心肌肥厚时中层心肌细胞跨膜动作电位复极达 90 %时程延长及心肌细胞瞬时外向钾电流、延迟整流钾电流下降较外膜和内膜细胞更为明显 ,使肥厚心肌跨室壁复极不均一性增大。缬沙坦预防性给药可抑制这一变化 ,     

自发性高血压大鼠左心室流出道自发性电活动的特征

利用玻璃微电极细胞内记录方法 ,记录了自发性高血压大鼠 (SHR)和Wistar鼠左心室流出道自发性慢电位和自发性快电位的特征。结果发现 ,SHR自发性快电位的动作电位时程 (APD)、复极至 5 0 %时间 (APD50 )和复极至 90 %的时间 (APD90 )均明显长于Wistar鼠 (P <0 0 1) ;SHR的自发放电频率 (RPF)明显慢于Wistar鼠 (P <0 0 5 )。结果提示 :SHR左心室流出道自发性的快电位和慢电位均表现为APD、APD50 和APD90 的延长 ,RPF减慢     

Ultrastructural changes during myocardial hypertrophy and its regression: Long-term effects of nifedipine in adult spontaneously hypertensive rats

Summary Nifedipine (20mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N,n=8). Comparison was done with sex-matched 15-week-old SHR (SHR-15,n=7), untreated 35-week-old SHR (SHR-C,n=10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15,n=15), and 35-week-old WKY (WKY-15,n=5). Light and electron microscopic data on the subepicardial, middle, and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199±11 mmHg vs 121±13mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.     

氯沙坦调节瞬间外向钾电流的分子学研究

目的 观察氯沙坦对自发性高血压大鼠(SHR)心室肌细胞编码瞬间外向钾电流(Ito)关键钾通道α亚基(Kv4.2、Kv4.3)、β亚基(KChIP2)mRNA和蛋白水平变化的影响,探讨氯沙坦抗室性心律失常效应的分子基础.方法 SHR随机分成2组:氯沙坦组(10 mg·d-1·kg-1灌胃)和SHR对照组各12只大鼠.鼠龄、体质量匹配的WKY大鼠12只为WKY对照组.用药8周后采用膜片钳技术记录左心室心肌细胞动作电位、Ito,并采用反转录聚合酶链反应及免疫印迹反应(Western blot)方法测定Kv4.2、Kv4.3、KChIP2 mRNA及蛋白水平.结果 氯沙坦组左心室细胞的动作电位复极至50%及90%时程分别为(16.82±3.79)ms和(68.49±13.25)ms,短于SHR对照组的(24.56±4.59)ms和(73.26±15.47)ms,二者差异有统计学意义(均P<0.01).氯沙坦组的Ito电流密度高于SHR对照组(从+40 mV到+70 mV,均P<0.01).氯沙坦组Kv4.2、Kv4.3 mRNA及蛋白水平高于SHR对照组(均P<0.01).氯沙坦组KChIP2 mRNA及蛋白水平低于SHR对照组(均P<0.01).结论 氯沙坦慢性阻滞血管紧张素受体,逆转SHR左心室的电重构,缩短单个心肌细胞动作电位时程,增加Ito电流密度,这与Kv4.2、Kv4.3表达增加及KChIP2表达降低相关.     

自发性高血压大鼠心脏重构与ACE2 mRNA的表达

目的:观察不同月龄的自发性高血压大鼠(SHR)的心脏血管紧张素转换酶2(ACE2)mRNA表达水平,探讨心脏重构与ACE2的内在联系。方法:将12周龄雄性SHR 18只和12周龄WKY Wistar-Kyoto rats大鼠18只随机分为两组,从WKY大鼠组和SHR组中各抽取9只处死,剩余的9只再喂养12周后处死。测量大鼠心脏的质量(HW)与体质量(BW)并计算HW/BW的比值。以实时定量RT-PCR法检测ACE2 mRNA的表达。结果:①与同周龄WKY大鼠组比较,SHR组HW/BW的比值显著增加(P0.01);与12周龄SHR组比较,24周龄SHR组的HW/BW显著增加(P0.05)。②与同周龄的WKY大鼠组比较,SHR组ACE2 mRNA的表达显著降低(P0.01);与12周龄的SHR组比较,24周龄的SHR组ACE2 mRNA的表达显著降低(P0.01)。结论:自发性高血压大鼠心脏重构伴随着心脏中ACE2 mRNA的表达下调。     

Relation between QRS amplitude and left ventricular mass in the initial stage of exercise-induced left ventricular hypertrophy in rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 +/- 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 +/- 0.02 mV, p < 0.001; SWIM 0.53 +/- 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 +/- 0.02 mV/g, p < 0.001; SWIM 0.55 +/- 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

Rate-Dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30–32 weeks

Summary We examined the characteristics of the action potentials of single ventricular myocytes obtained from the hearts of rats with chronicallyinduced diabetes. Male Wistar rats were made diabetic by injecting streptozotocin (65mg/kg) and 30–32 weeks later the hearts were excised and used for an electrophysiological study. Action potentials were recorded from isolated right ventricular myocytes by an electrode fabricated for patch clamp in the wholecell recording configuration. The action potential durations (APDs) of steady state chronic diabetic rat myocytes were longer than those of age-matched normal rat myocytes at all levels of repolarization (APD₂₅, APD₅₀, APD₇₅, and APD₉₀). As the stimulation frequency was increased (0.2–2Hz), the APDs were lengthened in both diabetic and normal rats, and the difference of APDs between the groups was greater when the stimulation frequency was higher. When we examined alterations of APDs under conditions of train stimulation (2Hz, 20 stimuli), (1) the APDs in both groups were prolonged, and (2) the degree of prolongation of APD was significantly greater and the rate of APD prolongation was significantly faster in myocytes from the diabetic rats. The prolongation of APD in these heart cells is probably secondary to alteration of the transient outward current I_to, and sheds light on repolarization abnormality in cases of diabetic cardiomyopathy.     

血管紧张素受体拮抗剂对SHR左室肥厚的影响

目的探讨血管紧张素Ⅱ受体（ＡＴＲ）拮抗剂在左室肥厚中的作用。方法自发性高血压大鼠（ＳＨＲ）分别接受ＴＣＶ－１１６（血管紧张素Ⅱ－１受体拮抗剂）、德那脯利（Ｄｅｌａｐｒｉｌ）及ＰＤ１２３３１９（血管紧张素Ⅱ－２受体拮抗剂）治疗３周,ＷＫＹ大鼠分别接受ＴＣＶ－１１６、Ｄｅｌａｐｒｉｌ治疗３周,分别与对照组比较收缩压及左室重量与体重比（ＬＶＷ／ＢＷ）。结果ＳＨＲ实验组：口服ＴＣＶ－１１６和Ｄｅｌａｐｒｉｌ分别使收缩压下降１８．５％和１９．０％,使ＬＶＷ／ＢＷ下降７．６％和８．３％;皮下注射ＰＤ１２３３１９对收缩压及ＬＶＷ／ＢＷ均无影响。ＷＫＹ实验组：口服ＴＣＶ－１１６和Ｄｅｌａｐｒｉｌ分别使收缩压下降１１．８％和１１．１％,对ＬＶＷ／ＢＷ无影响。结论血管紧张素Ⅱ－１型受体拮抗剂ＴＣＶ－１１６能逆转ＳＨＲ左室肥厚;血管紧张素Ⅱ－２型受体拮抗剂ＰＤ１２３３１９对ＳＨＲ左室肥厚无逆转作用。     

Relation Between QRS Amplitude and Left Ventricular Mass in the Initial Stage of Exercise-Induced Left Ventricular Hypertrophy in Rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRS_max to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 ± 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 ± 0.02 mV, p < 0.001; SWIM 0.53 ± 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 ± 0.02 mV/g, p < 0.001; SWIM 0.55 ± 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

低渗性肿胀对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响

观察单个豚鼠心室肌细胞动作电位和主要复极期电流延迟整流钾电流(IK)的变化,探讨急性心肌缺血再灌注室性心律失常发生的离子机制。采用全细胞膜片钳记录技术,观察低渗液(200mOsm/kg)灌流胶原酶分离的单个豚鼠心室肌细胞发生肿胀后的动作电位各参数的变化,同时记录IK及其快、慢两种激活成分(IKr及IKs)的变化。结果:低渗液灌流后心室肌细胞迅速发生肿胀,动作电位幅度(APA)、静息膜电位(RMP)及阈电位水平无明显变化;而动作电位时程(APD)在600,1000和3000ms三种基础起搏周长(BCL)刺激时均缩短(P<0.05),尤以APD复极达50%和90%时缩短更为明显。APD生理性频率适应性消失且离散度增大。低渗性肿胀状态下IK电流幅度在3000ms长去极化保持时间(主要成分为IKs)刺激时从1134.33±150.17pA增加至1621.98±234.95pA(P<0.001,n=10);而在100ms短去极化保持时间(主要成分为IKr)刺激时从693.44±96.44pA降低至294.06±71.79pA(P<0.05,n=8);并且使IK的IV曲线向上移位。结论:低渗性肿胀的心室肌细胞IK特别是IKs的增加是引起APD缩短的重要因素,是急性心肌缺血再灌注室性心律失常发生的离子机制之一。     

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。     

Endothelin-1-receptor-mediated responses in resistance vessels of young and adult spontaneously hypertensive rats

OBJECTIVE: To assess whether primary changes in endothelin-1 (ET-1) receptor responsiveness or secondary vessel functional modifications could characterize the effects evoked by ET-1 in the mesenteric vascular bed (MVB) of prehypertensive 5-week-old and 12-week-old spontaneously hypertensive rats (SHRs). DESIGN AND METHODS: We used male 5-week-old and 12-week-old SHRs and sex- and age-matched Wistar-Kyoto (WKY) rats as controls. ET-1 receptor responsiveness was evaluated by ET-1 (0.04-2 micromol/l) concentration-response curves and repeated with indomethacin and BQ-123 (0.1-0.5 micromol/l), the latter a selective ETA receptor antagonist. ETB receptor responsiveness was tested by sarafotoxin S6c (1-100 nmol/l) and IRL-1620 (0.1-10 nmol/l) concentration-response curves, obtained in the noradrenaline-precontracted MVB. RESULTS: At 5 weeks of age, ET-1 induced a similar concentration-dependent contraction in SHRs and WKY rats, with an overlapping BQ-123 pA2 value (negative common logarithm of the antagonist that produces an agonist dose ratio of 2) in the two strains. Indomethacin was ineffective in both groups. Sarafotoxin S6c and IRL-1620 both evoked an ETB-mediated, significant relaxation, only in WKY rats. In 12-week-old SHRs, ET-1 evoked a markedly increased maximal effect compared with the response in WKY rats (P< 0.01); this was prevented by treatment with indomethacin. The BQ-123 pA2 value was higher in SHRs than in WKY rats (P< 0.01). Both sarafotoxin S6c and IRL-1620 evoked a significant concentration-dependent relaxation in WKY rats, which was not detected in SHR preparations. CONCLUSIONS: Our results could suggest that the different responses evoked by ET-1 in the MVB of SHRs during the onset of hypertension may be related partially to primary alterations in the ET-1 receptorial pattern and partially to the onset of high blood pressure, leading to an impairment in the haemodynamic balance.