ATP敏感性钾通道的活化改善心肌顿抑的作用

为了解ＡＴＰ敏感性钾通道（ＫＡＴＰ）的活性对心肌顿抑进程的影响。本实验结扎家兔左冠状动脉左室支１０分钟后，再灌注２小时造成短暂缺血－再灌注心肌顿抑模型，观察心电图、血流动力学、抗氧化酶、脂质过氧化物及细胞Ｋ＋、Ｎａ＋、Ｃａ２＋的变化。结果，与对照组比较，活化ＫＡＴＰ通道能显著降低心脏后负荷（８０±７ｖｓ．１０２±１０，Ｐ＜０．０５）和心肌耗氧量（２．２±０．０５ｖｓ．２．７５±０．０９，Ｐ＜０．０１），逆转缺血心肌细胞内钙超载（２．４９±０．２８ｖｓ．０．９９±０．０８，Ｐ＜０．０１），提高再灌注期ＬＶｄｐ／ｄｔｍａｘ（４１．５％ｖｓ．８９％，Ｐ＜０．０１），降低ＭＤＡ浓度及ＭＤＡ／ＳＯＤ值（３．６±０．４ｖｓ．７．６±０．５，Ｐ＜０．０１；０．０９２±０．００８ｖｓ．０．２７０±０．０３４，Ｐ＜０．０１）。表明活化ＫＡＴＰ通道能产生直接的心肌保护作用，逆转心肌顿抑。     

不同龄SHR心肌细胞内Ca^2＋及心肌细胞NE含量的变化

采用荧光探针结合计算机图像处理技术测定幼年、成年、老年ＳＨＲ心肌单细胞内游离Ｃａ＾２＋浓度，采用高血压液相色谱法测定幼年、成年、老年ＳＨＲ心肌去甲肾上腺素含量。结果显示随着年龄增加，ＳＨＲ心肌细胞内游离Ｃａ＾２＋增加，而心肌组织ＮＥ含量下降。与老年ＷＫＹ大鼠比较，老年ＳＨＲ心肌细胞内Ｃａ＾２＋含量较高，而其心肌组织ＮＥ含量却较少。     

自发性高血压大鼠心肌乳酸盐转运障碍

目的在离体心脏灌流模型及分离的心肌肌膜囊泡上，比较自发性高血压大鼠（ＳＨＲ）和对照（Ｗｉｓｔａｒ－ＫｙｏｔｏＷＫＹ）大鼠心肌Ｌ－１４Ｃ－乳酸盐的摄入，及心肌肌膜囊泡（ＳＬＶ）对乳酸盐转运的特征。方法应用１４Ｃ标记的乳酸盐，测定ＳＨＲ和ＷＫＹ大鼠心肌ＳＬＶ的乳酸盐的转运。结果ＳＨＲ心肌摄取乳酸盐的能力较ＷＫＹ大鼠明显降低（４．２１±０．３１ｖｓ５．７２±０．３３ｎｍｏｌ／ｍｇＷＷ／２ｍｉｎ，Ｐ＜０．０１），ＳＬＶ的乳酸盐跨膜转运呈时间－浓度依赖性，ＳＨＲ较ＷＫＹ大鼠ＳＬＶ乳酸盐最大转运速率降低３６％（Ｐ＜０．０１），心肌乳酸盐的摄入和ＳＬＶ的转运速率与心肌肥大程度呈负相关（ｒ＝－０．６７，Ｐ＜０．０５，ｒ＝－０．７３，Ｐ＜０．０５）。结论ＳＨＲ大鼠存在心肌乳酸转运障碍     

血管利钠肽减弱去甲肾上腺素对心肌生长的刺激作用

本实验目的在于研究血管利钠肽（ Ｖ Ｎ Ｐ）对去甲肾上腺素（ Ｎ Ｅ）促心肌生长作用的影响,并对其机制进行探讨。分离、培养乳鼠心肌细胞,完全随机分为三组:对照组、 Ｎ Ｅ组和 Ｖ Ｎ Ｐ＋ Ｎ Ｅ组。以 Ｍ Ｔ Ｔ法和总蛋白含量测定法观察各组细胞的生长情况。进而采用放射免疫方法研究了 Ｖ Ｎ Ｐ对细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平的影响。结果发现: Ｎ Ｅ（１０－ ７ ｍ ｏｌ／ Ｌ～１０－ ５ ｍ ｏｌ／ Ｌ）可以使培养的乳鼠心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值显著升高（ Ｐ＜ ０．０５ ｖｓ 对照组）,并且具有剂量依赖性。 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）可以显著降低 Ｎ Ｅ（１０－ ６ ｍ ｏｌ／ Ｌ） 刺激的心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值和细胞内总蛋白含量（ Ｐ＜０．０５ ｖｓ Ｎ Ｅ组）。对照组和 Ｎ Ｅ组细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平无显著差异,而 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）能升高细胞内ｃ Ｇ Ｍ Ｐ水平,降低ｃ Ａ Ｍ Ｐ水平（ Ｐ＜ ０．０５ ｖｓ对照组、 Ｎ Ｅ组）。提示 Ｖ Ｎ Ｐ能减弱 Ｎ Ｅ对心肌生长的刺激作用,其机制可能与ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ等信号转导分子有关。     

家兔心肌缺血再灌注时中性粒细胞胞浆游离钙、MDA、SOD变化规律比较

目的通过对比观察青、老年家兔心肌缺血再灌注时外周血中性粒细胞（ＰＭＮｓ）胞浆游离钙（［Ｃａ~（２＋）］ｉ）、丙二醛（ＭＤＡ）及超氧化物歧化酶（ＳＯＤ）的变化规律，探索上述变化对老年兔心肌缺血再灌注损伤的影响特征，并寻找一种可替代心肌组织标本作为判断再灌注损伤的检测指标。方法５年龄及６月龄家兔实验性心肌缺血３０分钟、再灌注３０、９０、３６０分钟，分别取外周血ＰＭＮｓ及心肌组织测定ＭＤＡ、ＳＯＤ、ＰＭＮ［Ｃａ~（２＋）］ｉ和心肌组织钙。结果青、老年组ＰＭＮ［Ｃａ~（２＋）］ｉ、ＭＤＡ于缺血期均明显升高，至再灌注时更显著，而ＳＯＤ活性则明显降低（Ｐ值均＜０．０１）；上述改变在老年组更明显（Ｐ值＜０．０５及０．０１）。ＰＭＮ［Ｃａ~（２＋）］ｉ、ＭＤＡ、ＳＯＤ的变化分别与心肌钙、ＭＤＡ、ＳＯＤ的变化呈正相关（ｒ值分别为０．９２９２、０．９４３６和０．９８６７）。结论钙超载、氧自由基不但共同参与心肌缺血再灌注损伤，且老年期对致损因子更敏感。ＰＭＮｓ指标测定可作为判断心肌缺血再灌注损伤程度的可靠方法。     

NIDDM病人红细胞变形能力与红细胞ATP酶活性和红细胞内离子浓度关系的研究

本文检测了４２例ＮＩＤＤＭ病人红细胞变形能力（ＥＤ）和红细胞ＡＴＰ酶活性、红细胞内离子浓度的变化。结果显示ＮＩＤＤＭ病人红细胞滤过指数（ＩＦ）较对照组明显增高（Ｐ＜０．００１）；红细胞Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性较对照组明显降低（Ｐ＜０．０１），Ｍｇ２＋－ＡＴＰ酶活性变化不明显；红细胞内Ｎａ＋、Ｃａ２＋浓度较对照组明显增高（Ｐ＜０．０１），而Ｍｇ２＋浓度较对照组明显降低（Ｐ＜０．０１）。有血管病变者这些变化较无血管病变者更明显。ＮＩＤＤＭ病人红细胞ＩＦ与Ｎａ＋－Ｋ＋－ＡＴＰ酶、Ｃａ２＋－ＡＴＰ酶活性呈负相关（ｒ＝－０．４６８，－０．４５８，Ｐ＜０．００１），与红细胞内Ｎａ＋、Ｃａ２＋浓度呈正相关（ｒ＝－０．４７３，０．４６６，Ｐ＜０．Ｄ０１），与Ｍｇ２＋浓度呈负相关（ｒ＝－０．４３６，Ｐ＜０．０１）。     

信号平均心电图对冠心病的诊断价值

本文观察信号平均心电图（ＳＡＥＣＧ）对冠心病的诊断价值，对老年冠心病组和老年对照组的ＳＡＥＣＧ进行分析。老年冠心病组滤波后ＱＲＳ波时限（ＴＱＲＳ）、滤波后ＱＲＳ电压低于４０μＶ的时限（ＬＡＳ４０）、滤波后ＱＲＳ终末４０ｍｓ的平均平方根电压（ＲＭＳ４０）分别是１０４．４５±２０．０１ｍｓ、３０．６９±７．７１ｍｓ、３８．８８±６．７１μＶ，与老年对照组相比明显差异（分别为Ｐ＜０．０５、Ｐ＜０．０１、Ｐ＜０．０１）；在非老年人群中，超声运动负荷试验阳性（ＥＸＥ．Ｐ）组与对照组和超声运动负荷试验阴性（ＥＸＥ．Ｎ）组的ＴＱＲＳ、ＬＡＳ４０、ＲＭＳ４０对比，前组较后２组也存在明显差异（分别为Ｐ＜０．０１、Ｐ＜０．０５、Ｐ＜０．０１）。表明ＳＡＥＣＧ作为无创伤性和安全的方法，对冠心病的诊断具有一定的临床价值。     

严重充血性心力衰竭患者自主神经功能与心率变异的关系及地高辛的影响

对２５例重度充血性心力衰竭（ＣＨＦ）患者在地高辛治疗前后测定血浆去甲肾上腺素（ＮＥ）及心率变异（ＨＲＶ）。结果显示：ＮＥ基础值与ＨＲＶ时域指标基础水平均呈负相关（Ｐ＜０．０５或＜０．０１）。地高辛治疗前后的ＮＥ相比（２９１±８０ｐｇ／ｍｌｖｓ２１３±８２ｐｇ／ｍｌ），Ｐ＜０．００１。２４小时平均ＲＲ间期及２４小时正常ＲＲ间期标准差由治疗前的７２７±１２３ｍｓ及６７．７±２１．８ｍｓ分别增加至７７７±１２２ｍｓ及８７．２±２９．２ｍｓ（Ｐ均＜０．０５）；２４小时相邻ＲＲ间期差值的均方根（ＲＭＳＳＤ）、２４小时正常相邻ＲＲ间期之差大于５０ｍｓ的心搏数所占百分比（ＰＮＮ５０）及高频（ＨＦ）由治疗前的３６．３±３０．６ｍｓ、５．３±５．５％及３７．１±２１．２ｍｓ２分别增加至５６．１±４３．７ｍｓ、１０．８±１０．６％及７９．９±５８．２ｍｓ２（Ｐ值＜０．０５至＜０．０１）；低频（ＬＦ）由治疗前的１１８．９±１３３．２ｍｓ２增加至１７１．２±１７２．８ｍｓ２（Ｐ＜０．００５）；ＮＥ下降幅度与时域指标增加幅度均呈正相关。ＨＲＶ多数时域指标增加幅度及其绝对值与血清地高辛浓度呈正相关，以ＲＭＳＳＤ和ＰＮＮ５０尤为显著（Ｐ?     

高血压左心室肥厚与心肌原癌基因c-fos的表达

目的研究细胞核内原癌基因ｃ－ｆｏｓ在高血压左室肥厚（ＬＶＨ）发生、发展过程中的作用。方法采用两种高血压模型即自发性高血压大鼠（ＳＨＲ）和两肾一夹型（２Ｋ１Ｃ）肾血管性高血压大鼠，观察在高血压所致ＬＶＨ的不同阶段，收缩压（ＳＢＰ）、左室重／体重比（ＬＶＷ／ＢＷ）及左心室ｃ－ｆｏｓ基因表达水平的变化。结果ＳＨＲ在８～１０周龄时已有明显的高血压和ＬＶＨ，其ＳＢＰ与ＬＶＷ／ＢＷ均显著高于对照的ＷＫＹ大鼠，左心室ｃ－ｆｏｓ基因表达水平与ＷＫＹ大鼠相比，差异无显著性，但二者均较高。２０～２２周龄与４０～４２周龄时，ＳＨＲ的ＳＢＰ、ＬＶＷ／ＢＷ及左室ｃ－ｆｏｓ基因表达水平明显高于对照组ＷＫＹ大鼠。２Ｋ１Ｃ大鼠左肾动脉缩窄１周后就有明显的ＬＶＨ，其ＬＶＷ／ＢＷ较假手术组大鼠显著升高（２．９０±０．１３ｖｓ２．５７±０．１５，Ｐ＜０．０５），同时伴左室ｃ－ｆｏｓ基因的高表达，至术后３周、１０周仍保持较高水平。钙拮抗剂尼群地平和血管紧张素ＡＴ１受体拮抗剂ｌｏｓａｒｔａｎ治疗１０周后均可使２Ｋ１Ｃ大鼠左室ｃ－ｆｏｓ基因表达水平降低。结论心肌原癌基因ｃ－ｆｏｓ的高表达可能参与高血压ＬＶＨ的发生、发展过程。     

老年大鼠心肌肌浆网功能的改变

目的 探讨老年大鼠心肌肌浆网（ＳＲ）钙转运的改变及其在心脏收缩功能障碍中的作用。方法 测定老年和成年Ｗｉｓｔａｒ大鼠心功能。取左心室肌组织制备肌浆网膜,采用Ｍｉｌｌｉｐｏｒｅ滤过法测定心肌ＳＲＣａ＾２＋摄取、Ｃａ＾２＋释放和＾３Ｈ－Ｒｙａｎｏｄｉｎｅ受体结合,并测定心肌ＳＲＣａ＾２＋－ＡＴＰ酶活性。结果 与成年组比较,老年组大鼠左室舒张末压（ＬＶＥＤＰ）升高８２％（Ｐ〈０．０５）,左室内压变化速度     

Altered catecholamine contents in vascular and nonvascular tissues in genetically hypertensive rats

We have measured the catecholamine (CA) contents in hearts, mesenteric vasculature, abdominal aorta, inferior vena cava, vasa deferentia and salivary glands from genetically hypertensive rats (SHR) and normotensive Kyoto-Wistar rats (WKY). We noted differences between the norepinephrine (NE) contents of individual tissues from SHR and WKY rats and have used two different analytical procedures for the measurement of NE to confirm these differences. Comparisons between tissue contents of NE in SHR and WKY rats indicated a greater content of NE in the following tissues from the SHR: heart, mesenteric artery, abdominal aorta, inferior vena cava and vasa deferentia. A modest elevation of NE [but not epinephrine (E)] was observed in adrenal glands from SHR rats. The NE contents of salivary glands from SHR and WKY rats were indistinguishable from each other. The results suggest that there may exist a generalized increase in NE contents in the peripheral vasculature of SHR rats. Furthermore, this increase is also present in the vasa deferentia, but not the salivary gland. The results draw attention to altered concentrations of NE in vascular and selected nonvascular tissues in the SHR.     

Influence of cold-induced increases in sympathetic nerve activity on norepinephrine content in the vasculature of the spontaneously hypertensive rat

In spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), we have examined both the endogenous norepinephrine (NE) contents of caudal arteries, mesenteric arteries and cardiac tissue as well as the rates of decline of NE in these tissues after inhibition of NE synthesis. The endogenous NE contents of caudal and mesenteric arteries from SHR rats were greater than those from WKY rats. In contrast, the NE contents of hearts from SHR and WKY rats were similar. After synthesis inhibition with alpha-methyl-p-tyrosine (300 mg/kg i.p.), the NE contents of hearts and mesenteric arteries decreased in a monoexponential fashion. The rates of decline of NE were similar for corresponding tissues from SHR and WKY rats. Cold stress, reported to selectively activate sympathetic discharge, did not influence the rates of decline of NE in mesenteric arteries of either SHR or WKY animals. In contrast, cold exposure dramatically accelerated the rate of decline of NE in cardiac tissue from both SHR and WKY rats. It is concluded that in mesenteric arteries from SHR rats there is a larger pool of NE with turnover characteristics not dissimilar from that prevailing in vessels from normotensive animals. The failure of cold stress to modify the rates of decline of NE in mesenteric and caudal arteries of SHR and WKY rats suggests that these arteries are under considerable sympathetic influence at ambient temperature. The results support the view that the hypernoradrenergic innervation found in SHR blood vessels, together with normal functioning of the sympathetic nervous system, may have the potential for producing a heightened peripheral vascular resistance in this model.     

Influence of age on contractile response to insulin-like growth factor 1 in ventricular myocytes from spontaneously hypertensive rats

Evidence suggests a pathophysiological role of insulin-like growth factor 1 (IGF-1) in hypertension. Cardiac function is altered with advanced age, similar to hypertension. Accordingly, the effects of IGF-1 on cardiac myocyte shortening and intracellular Ca(2+) were evaluated in hypertension at different ages. Ventricular myocytes were isolated from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), aged 12 and 36 weeks. Mechanical and intracellular Ca(2+) properties were examined by edge-detection and fluorescence microscopy. At 12 weeks, IGF-1 (1 to 500 ng/mL) increased peak twitch amplitude (PTA) and FFI changes (DeltaFFI) in a dose-dependent manner in WKY myocytes, with maximal increases of 27.5% and 35.2%, respectively. However, IGF-1 failed to exert any action on PTA and DeltaFFI in the age-matched SHR myocytes. Interestingly, at 36 weeks, IGF-1 failed to exert any response in WKY myocytes but depressed both PTA and DeltaFFI in a dose-dependent manner in SHR myocytes, with maximal inhibitions of 40.5% and 16.1%, respectively. Myocytes from SHR or 36-week WKY were less sensitive to norepinephrine (1 micromol/L) and KCl (30 mmol/L). Pretreatment with nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L) did not alter the IGF-1-induced response in 12-week WKY myocytes but unmasked a positive action in 12-week SHR and 36-week WKY myocytes. L-NAME also significantly attenuated IGF-1-induced depression in 36-week SHR myocytes. In addition, the Ca(2+) channel opener Bay K8644 (1 micromol/L) abolished IGF-1-induced cardiac depression in 36-week SHR myocytes. Collectively, these results suggest that the IGF-1-induced cardiac contractile response was reduced with advanced age as well as with hypertension. Alterations in nitric oxide and intracellular Ca(2+) modulation may underlie, in part, the resistance to IGF-1 in hypertension and advanced age.     

Cross-talk between cardiac kappa-opioid and beta-adrenergic receptors in developing hypertensive rats

The kappa-opioid receptor exerts a negative modulatory action on the beta-adrenoceptor and the action is blunted in adult spontaneously hypertensive rats (SHR). In order to determine whether the blunted negative modulation of the beta-adrenoceptor by the kappa-opioid receptor contributes to the development of hypertension, the electrically induced intracellular calcium ([Ca2+]i) transient was measured in single ventricular myocytes of SHR at 4, 6, 8 and 13-week-old and the age-matched Wistar Kyoto (WKY) rats. The electrically induced [Ca2+]i transients were augmented by norepinephrine (NE), a beta-adrenoceptor agonist, over four-fold in WKY rats of all ages studied and in SHR of 4 and 6 weeks of age. The enhancing effect of NE in 8- and 13-week-old SHR was, however, only approximately three-fold, significantly lower than the corresponding values in age-matched WKY rats. Similarly, the electrically induced [Ca2+]i transients were also augmented by forskolin, an activator of adenylate cyclase, by approximately two-fold in WKY rats of all ages and SHR aged 4 and 6 weeks. In SHR aged 8 and 13 weeks, the effect of forskolin was only 1.5-fold, significantly lower than the two-fold increase in the corresponding WKY rats. The enhancing effects of NE and forskolin were attenuated by U50,488H, a selective kappa-opioid agonist, by approximately 50 and 25%, respectively, in both types of rats of all ages studied, with the exception of 13-week-old rats. In rats of this age group, the attenuations by U50,488H on the enhancing effects of NE and forskolin were 17 and 9% in SHR, respectively, significantly less than the corresponding 54 and 29% in WKY. The fact that attenuation of U50,488H on the enhancing effects of NE and forskolin only occurs in 13-week-old SHR when hypertension has been fully developed indicates that the attenuated inhibitory modulation of kappa-opioid receptor stimulation does not contribute to the initiation of hypertension. Interestingly, the enhancing effects of NE and forskolin on the electrically induced [Ca2+]i transient was attenuated in SHR aged from 8 weeks when the blood pressure was rapidly increasing. The different time courses of altered responses to U50,488H, and NE and forskolin suggest that the attenuated negative modulation of kappa-receptor stimulation on the beta-adrenergic receptor is not due to the signal transduction pathway activated by beta-adrenergic stimulation. In 13-week-old SHR with the arterial blood pressure restored to normal by pharmacological manipulations, the blunted responses to NE, U50,488H and forskolin still occurred, indicating that the altered responses to activation of beta-adrenergic and kappa-opioid receptors and adenylate cyclase are not secondary to hypertension.     

Gender-dependent difference in cell calcium handling in VSMC isolated from SHR: the effect of angiotensin II

OBJECTIVE: To investigate gender-dependent difference in the free cytosolic calcium concentration ([Ca2+ ]i ) response to angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR). To further evaluate this gender-dependent difference by studying the role of thapsigargin-sensitive intracellular calcium stores and calcium influx in VSMC isolated from male and female SHR. DESIGN AND METHODS: Confluent primary cultures of VSMC isolated from male (n = 14) and female (n = 14) SHR aged 10 weeks were used in this study. [Ca2+ ]i was measured by image analysis of single myocytes loaded with Fura-2. [Ca2+ ]i response of VSMC to Ang II was measured in the presence and absence of extracellular Ca2+, to evaluate the influence of Ca2+ influx. To characterize inositol triphosphate (IP3 )-sensitive sarcoplasmic reticulum calcium stores, thapsigargin-sensitive calcium stores were measured in VSMC isolated from SHR of both genders. RESULTS: VSMC isolated from male SHR were characterized by an augmented [Ca2+ ]i response to angiotensin II in comparison with VSMC isolated from female SHR. Surprisingly, the thapsigargin-stimulated [Ca2+ ]i rise was found to be significantly greater in VSMC isolated from female SHR compared with VSMC isolated from male SHR. On the other hand, the gender-dependent difference in [Ca2+ ]i response to angiotensin II was abolished in the absence of extracellular calcium. CONCLUSIONS: We demonstrated in VSMC isolated from SHR of both genders that a greater [Ca2+ ]i response to angiotensin II in male than female VSMC is dependent on Ca2+ influx.     

Increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in spontaneously hypertensive rats versus Wistar-Kyoto rats: relation to arteriosclerosis

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium-binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels, and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives our group showed increased calcium and a decreased magnesium and increased calcium/magnesium ratio in hypertensive cells.In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4 +/- 9.8 mm Hg) and 13 normotensive rats (NT, systolic blood pressure 118.5 +/- 7.2 mm Hg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick; the calcium content was 124.7 +/- 4.5 mmol/kg dry weight in SHR versus 110.3 +/- 4.1 mmol/kg dry weight in NT (mean +/- SD, P <.01 for both), the magnesium content was 35.5 +/- 3.9 in SHR versus 50.1 +/- 4.9 mmol/kg dry weight in NT (P <.01 for both). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56 +/- 3.9 versus 2.23 +/- 0.27 [P <.01 for both]). Thus, aortic smooth muscle cells from SHR are characterized by a markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. Cellular calcium and magnesium handling is disturbed in SHR aortic smooth muscle cells as it is in hypertensive blood cells. The increased calcium/magnesium ratio in hypertensive cells is a pathogenetic factor for the development of arteriosclerosis and hypertension.     

Contractile properties of ventricular myocytes isolated from spontaneously hypertensive rat.

OBJECTIVE: To determine whether there are any differences in contractile properties of individual cardiac myocytes isolated from the spontaneously hypertensive rat (SHR) in comparison with its normotensive control--the Wistar-Kyoto (WKY) rat. DESIGN: The effects of cardiac hypertrophy upon individual myocytes from SHR have not been studied previously. Isolated cardiac myocytes do not suffer from a number of problems inherent in experiments on multicellular preparations. METHODS: Seven SHR and eight WKY animals were studied. Age-matched animals were compared at 60 and 100 days old. Ventricular myocytes were isolated enzymatically. Myocyte length and width was measured. The cells were stimulated with extracellular electrodes and contraction was measured optically. The effects of altering stimulus rate and extracellular calcium concentration upon contraction were studied. RESULTS: SHR myocytes were found to be significantly wider than WKY myocytes. The contraction (i.e. unloaded cell shortening) of SHR myocytes at stimulation rate of 0.3, 1, 2 and 3 Hz was significantly increased. The time-course of contraction was altered, with SHR myocytes having an increased maximal velocity of shortening and relaxation. The response to changes in bathing calcium was similar in both strains. CONCLUSIONS: Individual cardiac myocytes isolated from SHR have an increased contraction. This indicates that cardiac hypertrophy, at least in the early stages, is a protective adaptation allowing the heart to overcome the increased afterload resulting from hypertension.     

A preliminary study on the cellular mechanism of hypotensive effect of high calcium diet in spontaneously hypertensive rats]

Significant reduction of both systolic blood pressure and body weight could be observed in SHRs after being fed with high calcium diet for about 7 weeks (P less than 0.01), with some changes of characteristics in ion transport in RBCs. The intracellular content of Na+, K+, the basic and calmodulin-stimulated activity of calcium-pump, and the calcium membrane binding ability on RBCs in SHR were determined. The intracellular content of K+ and the calmodulin-stimulated activity of calcium-pump in SHR fed with high calcium diet were significantly higher than those in SHR fed with normal calcium diet (P less than 0.01). The ratio of intracellular Na+ to K+ and the calcium membrane binding ability were found to be significantly reduced in SHR fed with high calcium diet (P less than 0.05). The systolic blood pressure in SHR fed with high calcium diet was found to be correlated inversely with the calmodulin-stimulated activity of calcium-pump and the intracellular K+ content (r = -0.720, r = -0.663 respectively, P less than 0.01). Thus, the hypotensive effect of chronic high calcium diet may be mediated through the changes in plasma ion transport, which most likely resulted from the changes in composition and structure of plasma membrane. The exact mechanism concerning the reduced calcium membrane binding ability in SHR fed with high calcium diet still remained unknown.     

黄芪总黄酮对心肌细胞内游离钙离子浓度的影响

目的研究黄芪总黄酮（Total flavonoids of Ast ragalus,TFA）对体外培养的乳鼠心肌细胞内游离钙离子浓度的作用。方法实验应用钙离子荧光指示剂Fluo-3AM负载原代培养的乳鼠心肌细胞,通过激光共聚焦扫描显微镜上机检测,记录其荧光强度变化,同时观察黄芪总黄酮对乳鼠心肌细胞及化学处理因素H2O2损伤大鼠心肌细胞的荧光强度的作用。结果①H2O2损伤的乳鼠心肌细胞游离钙离子[Ca^2＋]i平均荧光强度值为（1346．89±65．36）nmol／L,与对照组平均荧光强度值（743．15±34．78）nmol／L相比,差异有统计学意义（P〈0．01,n=7）;同时H2O2（0．3mmol／L）使予给TFA（20mg／kg）组乳鼠心肌细胞的[Ca^2＋]i平均荧光强度值由（668．29±41．15）nmol／L下降到（649．31±39．17）nmol／L,差异无统计学意义（P〉0．05,n=7）。结论H2O2可明显升高乳鼠心肌细胞游离钙离子浓度,黄芪总黄酮可对抗H2O2的这种作用。     

Valsartan prevents the development of rabbit's heart failure by restoring calcium uptake of sarcoplasmic reticulum

Objective Clinical evidence has suggested that ATI receptor blocker (ARB) could prevent the development of heart failure. Decreased sareoplasmic reticulum(SR) Ca2+ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups: sham rabbits(controls, n= 11), rabbits with heart failure treated with Valsartan (n= 11) and rabbits with heart failure but without Valsartan treatment (n=8).Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography. SR calcium uptake was determined by measuring extra vesicular free [Ca2+] changes in a fluores-cence spectrophotometer. SERCA2a, Serl 6-phosphorylated phospholamban (p-PLB), PKA and PP1a protein abundance were deter-mined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased (P<0.05), these changes could be significantly attenuated by Valsanan treatment (P<0.05).Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes (P<0.05), with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP1αin ventricular samples from the failing rabbits (P<0.05). All of these changes were attenuated by Valsartan treatment (all P<0.05). Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins.