膈肌疲劳与肌凝蛋白重链

膈肌疲劳在COPD及呼吸衰竭的发生机制中有重要意义。膈肌收缩功能受多种重要收缩蛋白分子的调节。其中 ,肌凝蛋白重链更具有特殊的生理及病理意义。本文对膈肌疲劳的相关因素及各种病理情况下膈肌的微观变化、膈肌疲劳与肌凝蛋白重链的关系以及有关药物对膈肌疲劳的作用等进行了综述。     

获得性漏斗胸膈肌肌凝蛋白重链MyHC-Ⅰ的表达变化和意义

目的通过检测获得性漏斗胸大鼠膈肌肌凝蛋白重链MyHC-Ⅰ的表达变化,探讨肌凝蛋白重链在获得性漏斗胸发生发展中的作用。方法选用4周龄SD大鼠48只,随机分为3组,每组16只。其中肋软骨组和膈肌组分别为从胸骨旁切断下位3对肋软骨并造成膈肌局部物理损伤而获得漏斗胸模型,对照组不做任何干预。于术后第2周和第4周每组各处死大鼠8只,收集膈肌组织,分别进行RT-PCR定量和Western blot检测。结果肋软骨组和膈肌组动物均呈现前胸壁凹陷畸形。与对照组比较,肋软骨组和膈肌组各时间点MyHC-Ⅰ表达均升高(P<0.05);但肋软骨组和膈肌组组间比较,仅术后第2周时MyHC-Ⅰ表达差异有统计学意义(P<0.05)。结论获得性漏斗胸动物膈肌肌凝蛋白重链MyHC-Ⅰ表达增高,说明在动物漏斗胸畸形形成过程中膈肌功能发生了改变。     

膈肌疲劳与肌凝蛋白重链

膈肌疲劳在COPD及呼吸衰竭的发生机制中有重要意义。膈肌收缩功能受多种重要收缩蛋白分子的调节。其中，肌凝蛋白重链更具有特殊的生理及病理意义。本文对膈肌疲劳的相关因素及各种病理情况下膈肌的微观变化、膈肌疲劳与肌凝蛋白重链的关系以及有关药物对膈肌疲劳的作用等进行了综述。     

心肌肌凝蛋白重链启动子的心血管组织特异性基因表达及其活性

目的　探讨心肌肌凝蛋白重链 (cMHC)基因启动子的心血管组织特异性及其表达活性 ,构建心血管组织靶向性表达的基因载体。方法　分别采用PCR法合成大鼠cMHC基因启动子片段 (- 16 0 0～ 32 )和酶切法获得CMV启动子片段 ,以取代 pAdSV4nlacZ载体中的LTR启动子 ,获得pAdSV4nlacZ、pAdMHCnlacZ和 pAdCMVnlacZ。上述载体分别转染培养的大鼠血管平滑肌细胞(VSMC)、心肌细胞 (CM )、心肌成纤维细胞 (CF)和人胚肾细胞 (2 93细胞 ) ,观察lacZ基因在上述细胞中的表达活性。结果　β-半乳糖苷酶活性在 pAdSV4nlacZ和 pAdCMVnlacZ转染的各组细胞间无显著差异 ;pAdMHCnlacZ在转染的CM中lacZ基因的表达明显高于其他各组细胞 ,β -半乳糖苷酶活性在VSMC组低于CM组 ,高于CF和 2 93细胞 (P <0 0 1) ,在CF和 2 93细胞间无差异 (P >0 0 5 )。结论　cMHC启动子的转录活性相对低于CMV启动子和LTR启动子 ,而在CM和VSMC中的表达活性高于CF和 2 93细胞 ,具有良好的心血管组织定向表达能力 ,适合用于心血管疾病的基因治疗。     

肥厚性心肌病患者心脏β—肌凝蛋白重链基因点突变的研究

应用聚合酶链式反应与ＤＮＡ单链构象多态技术，分析３２例肥厚性心肌病患者心脏β－肌凝蛋白重链基因第１３、１６、２０和２３外显子区域，发现１例患者第１３外显子ＰＣＲ产物的单链电泳带与正常对照有明显的差异。对其核苷酸顺序分析表明，该患者β－ＭＨＣ基因第３８３密码子位置发生Ｇ－Ｔ颠换，导致赖氨酸变成天冬酰胺。     

家族性肥厚型心肌病β型肌凝蛋白重链基因突变研究

1990年Tanigawa等连续报道了β-MHC的错义突变与FHC有关,这些突变集中在β-MHC的10个外显子,即外显子5,9,13,14,15,16,19,20,21,23.本文设计了9对PCR引物,限制性扩增β-MHC基因突变集中发生的9个外显子,用两轮扩增提高扩增产量,两步扩增法提高扩增产物的特异性.产物在中性聚丙烯酰胺上电泳进行SSCP分析.对6个肥厚型心肌病家系进行了β-MHC突变分析,结果显示,6个肥厚型心肌病家系中无一个家系找到β-MHC突变,表明突变的机率比国外报道的明显的低.     

抗心肌肌凝蛋白抗体在心脏疾病诊断中的应用

抗心肌肌凝蛋白抗体在心脏疾病诊断中的应用第二军医大学长海医院心内科秦永文综述章同华，陈思聪审校应用抗心肌肌凝蛋白抗体（ａｍｔｉｃａｒｄｉａｃｍｙｏｓｉｎａｎｔｉｂｏｄｙ，ＡｃＭＡ）进行心肌核素显像诊断心肌病变是近十多年发展起来的新技术。临床上已应用于...     

人心肌肌凝蛋白轻链的生化特性及其临床意义

测定人心肌肌凝蛋白（Ｍｙｏｓｉｎ）、肌凝蛋白轻链（Ｍ－ＬＣ）、重链（Ｍ－ＨＣ）的ＡＴＰ酶活性，结果Ｍ－ＬＣ的Ｍ－ＬＣＡＴＰ酶活性略高于肌凝蛋白ＡＴＰ酶活性，Ｍ－ＨＣ无ＡＴＰ酶活性。同时采用ＥＬＩＳＡ方法测定９６例正常人及４７例心肌梗塞病人，结果正常人血清Ｍ－ＬＣ１平均值为５．９６ｎｇ／ｍｌ，心肌梗塞病人为７３．５ｎｇ／ｍｌ（Ｐ＜０．００１）。心肌酶谱与Ｍ－ＬＣ１对心肌梗塞诊断符合率比较，Ｍ－ＬＣ１诊断符合率为１００％，ＣＰＫ同功酶ＭＢ为９０．６％。本组制备的单抗与兔心肌肌凝蛋白无交叉反应，抗鸡心肌Ｍ－ＬＣ的单抗与本组提纯的Ｍ－ＬＣ１亦无亲和反应，说明人心肌Ｍ－ＬＣ１单抗具有种属特异性。     

人心肌肌凝蛋白轻链的生化特性及其临床意义

测定人心肌肌凝蛋白、肌凝蛋白轻链、重链的ＡＴＰ酶活性。结果Ｍ－ＬＣ的Ｍ－ＬＣ ＡＴＰ酶活性略高于肌凝蛋白ＡＴＰ酶活性，Ｍ－ＬＣ无ＡＴＰ酶活性。同时采用ＥＬＩＳＡ方法测定９６例正常人及４７例心肌梗塞病人，结果正常人血清Ｍ－ＬＳ１平均值为５．９６ｎｇ．ｍｌ，心肌梗塞病人为７３．５ｎｇ／ｍｌ。     

Hormonal influences on cardiac myosin ATPase activity and myosin isoenzyme distribution

It has been recognized for a long time that changes in hormone secretion can influence cardiac function; however, the biochemical basis for these changes has only recently been clarified. In this review the influences of hormonal status on the contractile protein myosin is discussed. Myosin has a rod-like portion and a globular head and consists of two myosin heavy chains (MHC) and four light chains (LC), two of which are identical. The globular head is the site of an ATP-splitting enzyme, the myosin ATPase, and increases in myosin ATPase activity are closely related to an increased velocity of contraction of the heart. Myosin ATPase activity shows marked response to alterations in thyroid hormone, insulin, glucocorticoid, testosterone and catecholamine levels, but marked animal species differences in this response occur. Thyroid hormone administration to normal rabbits, for example, increases myosin ATPase activity markedly, but the myosin ATPase activity of hyperthyroid rats remains unchanged. In contrast, in hypothyroid rats myosin ATPase activity is markedly decreased but the hypothyroid rabbit shows no such response. These species-related differences in the hormonal response of myosin ATPase activity result from the predominance pattern of specific myosin isoenzymes. In the normal rat heart three myosin isoenzymes, v₁, V₂ and V₃, can be separated electrophoretically. Myosin V₁ predominates (70% of total myosin), and has the highest myosin ATPase activity, whereas in rabbits myosin v₃, which has a lower myosin ATPase activity, is the predominant isomyosin. Thyroid hormone administration to rabbits induces myosin V₁ predominance and therefore increases myosin ATPase activity, whereas in hyperthyroid rats only a small further increase in V₁ predominance can occur. The alterations in myosin isoenzyme predominance and myosin ATPase activity are closely correlated to changes in cardiac contractility. Hormone-induced alterations in myosin isoenzyme predominance are mediated through changes in the formation of two isoforms of myosin heavy chain. Changes in the expression of different myosin heavy chain genes are most likely responsible for the thyroid hormone and insulin-induced alterations in myosin isoenzyme predominance. Investigation of the control of myosin heavy chain formation can provide further insights into the hormonal control of a multigene family as well as broaden our understanding of the molecular events which result in altered cardiac contractility. It is currently unclear if androgens, glucocorticoids and catecholamines influence myosin ATPase activity through changes in myosin isoenzyme predominance resulting from alterations in myosin heavy chain gene expression. Post-translational modifications of myosin heavy chain and light chain polypeptides have also to be considered.     

Interaction of cardiac myosin and its light chains with calcium ions and regulation of binding by phosphorylation

The binding of calcium ions to cardiac myosin and to its isolated light chains has been measured and related to the state of phosphorylation. Isolated cardiac metal-binding light chains (LC₂) undergo a change in conformation when calcium or magnesium ions are added at physiological ionic strength. This can be followed by circular dichroism, which reveals that saturation with calcium under these conditions increases the α-helicity of the chain from about 27 to 34%. The profile is too steep to be accounted for in terms of a single titrating site, and there is evidently interaction between the primary binding site and weaker sites. The mid-point of the profile occurs at 0.6 μm and 1.25 μm free calcium concentration when the light chains are in the dephosphorylated and phosphorylated states respectively. In intact cardiac myosin the degree of saturation with calcium could be evaluated from the fractional protection of proteolytically labile sites. The level of protection conferred by bound calcium ions was critically dependent on the identity of the supporting electrolyte, ammonium acetate being particularly favourable. Calcium binding profiles were obtained at ionic strengths equivalent to physiological. They were consistent with the presence of independently titrating isolated sites. Again the affinity was appreciably perturbed by phosphorylation. Association constants of 5 × 10⁶ and 3 × 10⁶m^?1 were obtained for fully dephosphorylated and largely (but not completely) phosphorylated myosins respectively. These are compared with earlier published values, which vary over a range of 2 to 3 orders of magnitude. The circumstances under which the saturation of the metal binding sites could occur in the physiological milieu are considered.     

Involvement of Ras-regulated myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats

BACKGROUND: Early treatment with captopril prevents the development of hypertension by inhibiting the generation of angiotensin II and smooth muscle contraction. Although smooth muscle contraction is regulated by myosin light chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in hypertension has not been described. Therefore, we treated spontaneously hypertensive rats (SHR) with captopril and investigated the effects of this agent on downstream signaling. METHODS: Male SHR (n = 12) were treated with captopril (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used as controls. Rats were split into three subgroups and were sacrificed at 12, 18, or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body weight were measured. Mesenteric arteries were removed for histologic and biochemical studies. RESULTS: At 12 weeks, captopril significantly decreased systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08 mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light chain kinase (MLCK) expression, and MLC-P were all significantly increased in mesenteric arteries in untreated SHR compared with WKY rats. Early captopril treatment in SHR significantly inhibited Ras and MLCK expression at all ages and decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries. CONCLUSIONS: These data demonstrate that the antihypertensive effects of captopril are correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and MLC-P.     

风湿性心脏病心肌肌球蛋白轻链的变化及其对心功能的影响

目的 探讨风湿性心脏病（ＲＨＤ）并心力衰竭患心肌肌球蛋白轻链（ＶＭＬＣ）的变化及其对心功能的影响。方法 采用蛋白印迹杂交技术对１３例ＲＨＤ心力衰竭患心室肌中ＶＭＬＣ－１、２含量及组成比例进行定量分析;术前心功能指标采用肺动脉漂浮导管进行检测;采用ｔ检验及相关分析方法进行分析。结果 ＶＭＬＣ－１、２相对含量ＲＨＤ组较正常对照组显下降,尤以ＶＭＬＣ－２含量下降最为显;ＶＭＬＣ－１、ＶＭＬＣ－２     

Malalignment of the sarcomeric filaments in hypertrophic cardiomyopathy with cardiac myosin heavy chain gene mutation

OBJECTIVE—To investigate changes in the alignment of the sarcomeric filaments in hypertrophic cardiomyopathy and the effects of cardiac β myosin heavy chain (β-MHC) mutation on the sarcomeric ultrastructure.
DESIGN—A retrospective analysis.
PATIENTS—Endomyocardial biopsy samples were examined by transmission electron microscopy in seven patients with hypertrophic cardiomyopathy and β-MHC mutation, six with hypertrophic cardiomyopathy but without the mutation, and five controls (with chest pain syndromes).
MAIN OUTCOME MEASURE—Alignment of the sarcomeric filaments and the distance between neighbouring thick myosin filaments.
RESULTS—In controls, cross sections of the sarcomere at the A band showed a highly organised orthohexagonal array with 6 thin actin filaments surrounding one thick myosin filament, whereas in hypertrophic cardiomyopathy the alignment of the sarcomeric filaments was sparse and disrupted. In hypertrophic cardiomyopathy with a mutation, the distance between neighbouring thick myosin filaments was greater than in controls (mean (SD) 45.3 (4.7) v 38.5 (3.5) nm, p < 0.05), and the variance of the distance was greater than in controls (8.0 (0.7) v 4.8 (1.0) nm, p < 0.001) or in patients with hypertrophic cardiomyopathy without a mutation (6.7 (0.6) nm, p < 0.05). In the latter, the variance of the distance was also greater than in the controls (p < 0.01). A significant correlation was found between the grade of the myocyte hypertrophy and the variance of the distance (r = 0.654; p < 0.01).
CONCLUSIONS—The alignment of the sarcomeric filaments is disrupted in hypertrophic cardiomyopathy, particularly when there is β-MHC mutation.


Keywords: hypertrophic cardiomyopathy; β myosin heavy chain; myosin filament; sarcomere     

Isoforms of heavy and light chains of cardiac myosins from rat and rabbit

Summary The light chains of myosin from atrial and ventricular tissues from rat and rabbit were examined by one- and two-dimensional polyacrylamide gel electrophoresis. The myosin heavy chains were electrophoretically isolated, digested after denaturation in sodium dodecyl sulfate with papain and proteinase from S. aureus V8, and the resulting peptides resolved in one-dimensional gel electrophoresis.The peptide patterns of myosin heavy chains from atrial and ventricular tissues of adult rabbits were different, indicating differences in their primary structures. No such differences could be detected in a total of around 180 peptides produced by the two proteinases from the myosin heavy chains of adult rat atrial and ventricular tissues.With regard to light chains, the same migration pattern was observed for atrial and ventricular tissues from both rat and rabbit. The atrial light chains ALC1 and ALC2 migrated with molecular weights lying between those of the ventricular light chains VLC1 and VLC2. In two-dimensional electrophoresis, the corresponding light chains from rat and rabbit co-migrated. An additional light chain was observed in foetal ventricles, which exhibited identical electrophoretic properties to ALC1 from adult atrial tissues.In rat myofibrillar preparations from atrium and ventricle, an unidentified protein (x) occurred in the region of light chain-1 but with a more acidic isoelectric point, which seems to be related to the developmental stage of these tissues and which could not be detected in rabbit heart tissues or in any skeletal muscles.

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Zusammenfassung Die leichten Ketten von Myosin aus Atrium- und Ventrikelmyokard von Ratten und Kaninchen wurden in ein- und zweidimensionaler Polyacrylamidgel-Elektrophorese untersucht. Die schweren Ketten des Myosins wurden elektrophoretisch aufgetrennt, isoliert und nach Denaturierung in Natriumdodecylsulfat mit Papain und Proteinase von S. aureus V8 verdaut. Die Peptidgemische wurden in eindimensionaler Gel-Elektrophorese aufgetrennt. Die Peptidmuster der schweren Myosinketten aus Atrium und Ventrikel adulter Kaninchen unterscheiden sich; damit sind die entsprechenden Aminosäuresequenzen verschieden. Bei der Ratte fand sich kein Unterschied in den etwa 180 unterscheidbaren Peptiden von atrialen und ventrikulären schweren Myosinketten nach Verdauung mit beiden Proteinasen. Die leichten Myosinketten aus Atrium und Ventrikel von Ratten und Kaninchen zeigten in ein- und zweidimensionaler Elektrophorese identische Beweglichkeiten. Die elektrophoretisch bestimmten Molekulargewichte der atrialen leichten Ketten liegen zwischen denjenigen der leichten Ketten aus dem Ventrikel. Bei fetalen Ratten und Kaninchen ist im Ventrikelmyokard eine zusätzliche leichte Kette vorhanden, deren elektrophoretischen Eigenschaften identisch mit denen der adulten atrialen leichten Kette-1 sind. Bei adulten Ratten fanden wir im Atrium und im Ventrikel ein zusätzliches myofibrilläres Protein (x) mit ähnlichem Molekulargewicht wie die leichten Ketten-1, aber mit einem mehr im Sauren liegenden isoelektrischen Punkt. Dieses Protein (x) ist im fetalen Myokardgewebe nicht vorhanden und verschwindet bei alten Ratten wieder; wir fanden es nicht im Myokard von Kaninchen oder in irgendwelchen Skelettmuskeln.

     

Size and speed of the working stroke of cardiac myosin in situ

The power in the myocardium sarcomere is generated by two bipolar arrays of the motor protein cardiac myosin II extending from the thick filament and pulling the thin, actin-containing filaments from the opposite sides of the sarcomere. Despite the interest in the definition of myosin-based cardiomyopathies, no study has yet been able to determine the mechanokinetic properties of this motor protein in situ. Sarcomere-level mechanics recorded by a striation follower is used in electrically stimulated intact ventricular trabeculae from the rat heart to determine the isotonic velocity transient following a stepwise reduction in force from the isometric peak force T_P to a value T (0.8–0.2 T_P). The size and the speed of the early rapid shortening (the isotonic working stroke) increase by reducing T from ∼3 nm per half-sarcomere (hs) and 1,000 s⁻¹ at high load to ∼8 nm⋅hs⁻¹ and 6,000 s⁻¹ at low load. Increases in sarcomere length (1.9–2.2 μm) and external [Ca²⁺]_o (1–2.5 mM), which produce an increase of T_P, do not affect the dependence on T, normalized for T_P, of the size and speed of the working stroke. Thus, length- and Ca²⁺-dependent increase of T_P and power in the heart can solely be explained by modulation of the number of myosin motors, an emergent property of their array arrangement. The motor working stroke is similar to that of skeletal muscle myosin, whereas its speed is about three times slower. A new powerful tool for investigations and therapies of myosin-based cardiomyopathies is now within our reach.The performance of heart depends on the power developed by the myocardium, which in turn is strongly dependent on the end-diastolic volume modulating the systolic pressure development (Frank–Starling law of the heart). At the level of the sarcomere, the structural unit of striated muscle, the Frank–Starling law originates from the increase in the force of contraction with an increase in sarcomere length (length-dependent activation). Mutations of sarcomere proteins affect power output and are considered responsible for various forms of cardiomyopathy (1, 2). Over 250 mutations in cardiac myosin II have been reported as the cause of cardiomyopathies (1, 3, 4). Defining the mechanokinetic properties of the cardiac myosin in situ is therefore fundamental to understand the pathomechanisms of these cardiomyopathies and to provide previously unidentified therapeutic opportunities.In the sarcomere, the myosin motors are organized in two bipolar arrays extending from the thick filament and pulling the thin actin-containing filaments from the opposite sides of the sarcomere toward its center. In each array, the myosin motors are connected in parallel via their attachments to the thick filament and the resulting collective motor provides steady force and shortening by cyclic asynchronous ATP-driven actin–myosin interactions. Thus, the performance of the heart relies on the integration of the mechanokinetic properties of the myosin motor and the properties emerging from its array arrangement in the half-sarcomere (hs). Using sarcomere-level mechanics in intact cells from the skeletal muscle, it has been shown that the isotonic velocity transient following stepwise changes in force imposed on the otherwise isometric contraction contains information on both the working stroke of the myosin motor and the steady-state force–velocity (T–V) relation resulting from the cyclic actin–myosin interactions and accounting for the power output (5–9).Here, this approach is applied for the first time (to our knowledge) to a multicellular cardiac preparation like the intact trabecula dissected from the right ventricle of the rat heart. A striation follower (10) proved to be a reliable tool for measurement of sarcomere length changes with nanometer–microsecond resolution owing to optical averaging of the image of the sarcomeres that reduces the background noise originating from intracellular and intercellular components of the trabecula. Following the original idea by ter Keurs et al. (11), the sarcomere shortening recorded during the force development in a fixed-end twitch is used as a feedforward signal to maintain sarcomere length constant during the next twitch. By switching from length control to force control, a stepwise drop in force was imposed at the peak of force (T_P) to record the isotonic velocity transient. In this way, the amplitude and speed of the rapid phase of the transient (phase 2), which is the mechanical manifestation of the myosin working stroke, could be determined. Increases in sarcomere length (SL) from 1.9 to 2.2 μm and in the external Ca²⁺ concentration ([Ca²⁺]_o) from 1 to 2.5 mM, which produce an increase in T_P, do not affect the myosin working stroke. This indicates that length-dependent potentiation of cardiac contractility is fully accounted for by an increase in the number of attached myosin motors. These experiments demonstrate that our sarcomere-level mechanical methods have the full potential for the in situ investigation of cardiomyopathy-causing mutations in cardiac myosin.     

卡托普利联合舒血宁治疗老年原发性高血压急症的疗效

目的 观察卡托普利联合舒血宁治疗老年原发性高血压（高血压）急症的临床疗效.方法 选择老年高血压急症患者共106例,分为治疗组和对照组各53例.两组患者均舌下含服卡托普利25 mg,治疗组加用舒血宁注射液20 mL加入250 mL 5％葡萄糖注射液（糖尿病患者改为0.9％氯化钠注射液）静脉注射.比较两组治疗前、后的血压、心率、心电图、临床症状及不良反应等.结果 治疗组治疗后不同时间点的舒张压和收缩压下降均比对照组明显,差异有统计学意义（P＜0.05）.治疗组治疗总有效率明显高于对照组,差异有统计学意义[94.33％（50/53）vs.67.92％（36/53）,P＜0.05].结论 卡托普利联合舒血宁治疗老年高血压急症较单纯应用卡托普利治疗更具优势,疗效较好.     

Cardiac myosin phenotype remodelling following adrenodemedullectomy and chronic 6-hydroxydopamine in male Sprague-Dawley rats

BACKGROUND:

An increase was previously found in relative beta myosin heavy chain (MyHC) in the right ventricle of rats following thoracic spinal transection. It was hypothesized that the MyHC remodelling that was observed might be due, in part, to autonomic influences on the right ventricle.

OBJECTIVE:

To evaluate cardiac myosin phenotype following 21 days of reduced sympathetic activity.

METHODS:

Adult male Sprague-Dawley rats underwent either adrenodemedullectomy/chemical sympathectomy (SX) or sham operation/sham injection (CN). Twenty-one days following surgery, the animals were sacrificed and both ventricles were harvested. The ventricles were denatured and run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis for identification of MyHC isoforms.

RESULTS:

SX resulted in a significant decline in catecholamines. In the right ventricle, beta MyHC ratio was twofold higher in SX animals than in CN rats, but there was no difference between groups in beta MyHC concentration in the left ventricle (P<0.05). Uniquely, we found a decrease in relative alpha MyHC in the right ventricle but no change in the myosin phenotype in the left ventricle.

CONCLUSIONS:

These data potentially indicate that MyHC concentrations in the left ventricle are less sensitive than the right ventricle to decreased sympathetic activity.     

动脉血压在肾性高血压大鼠心肌α-和β肌球蛋白重链基因表达中的作用

本实验用肾性高血压大鼠模型,探讨动脉血压在心肌肥厚和肌球蛋白重链(Myosinheavy chain,MHC)基因表达中的作用.结果表明:(1)二肾二夹(2K1C)肾性高血压大鼠,术后48～72h,血压升高.α-MHC基因表达减弱,β-MHC基因表达增强,左室重量/体重(LVW/BW)比值变化不明显;(2)二肾一夹(2K1C)肾性高血压大鼠术后第2～12w,动脉血压持续升高,LVW/BW比值明显升高,左心室α-MHC基因表达明显减弱,β-MHC基因表达明显增强;(3)血管紧张素转换酶抑制剂、巯甲丙脯酸可使2K1C肾性高血压大鼠动脉血压下降,左室肥厚发生逆转,抑制左心室α-MHC基因表达减弱和β-MHC基因表达增强.这些结果提示,在肾性高血压过程中,动脉血压升高是左心室肥厚、左室心肌MHC基因转换(switch)的重要因素,肾素-血管紧张素系统可能参与肾性高血压过程中的心肌肥厚和MHC基因转换.