Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats.

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.     

氯沙坦逆转高血压大鼠心肌重塑的实验研究

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌重塑的影响。方法16周龄雄性SHR20只,随机分为氯沙坦治疗组和SHR对照组。同龄雄性WKY鼠10只作为正常对照组。给予氯沙坦每天30mg/kg溶于饮水灌胃治疗17周。测定动脉收缩压、左心室壁的厚度、左心室重量与体重之比(LVW/BW)。透射电镜评估左心室肥厚(LVH)的程度。用真彩色图像分析系统计算左心室胶原容积分数。结果氯沙坦治疗组血压、LVW/BW、左室壁厚度与SHR对照组相比明显降低,但与WKY相比有所升高。透射电镜下氯沙坦治疗组心肌的超微结构与WKY相似,SHR的结构有异常改变。与SHR对照组相比,氯沙坦治疗组左心室胶原容积分数下降。结论氯沙坦能有效地降低SHR的血压、逆转高血压左室重塑。     

SHR心肌细胞内钙离子浓度改变与左室肥厚和功能的关系

目的:探讨自发性高血压大鼠(SHR)心肌细胞内钙离子浓度的动态演变规律及其与左室肥厚和功能的相互关系。方法:应用Ca²⁺荧光指示剂Fura-2/AM分别测定了10周龄、22周龄、34周龄SHR心肌细胞内Ca²⁺浓度以及导管法测定了大鼠心功能,并以同龄京都-Wistar(WKY)大鼠作对照。结果:各周龄SHR收缩压(SBP)、心肌细胞内Ca²⁺浓度([Ca⁺]_i)、左室重量/体重(LVM/BW)均明显高于同龄正常血压WKY大鼠,22周龄SHR左室压力最大下降速率(-dp/dt_max)低于、左室松弛时间常数(τ)长于同龄WKY大鼠,34周龄SHR±dp／dt_max和左室收缩指数均显著低于同龄WKY大鼠,τ进一步延长;心肌细胞内[Ca⁺]_i与大鼠LVM/BW、SBP-dp／dt_max、τ呈显著正相关(r=0.47-0.83,P＜0.01),与dp／dt_max和收缩指数呈显著负相关(r=-0.46,P<0.05和-0.81,P<0.01)。结论:SHR心肌细胞内钙离子超负荷不仅介导了心肌肥厚的形成,还导致了心肌的收缩和舒张功能障碍。     

盐酸莫索尼定对自发性高血压大鼠左室肥厚的影响

目的:研究国产盐酸莫索尼定对自发性高血压大鼠左室肥厚时心肌纤维化和冠状动脉微血管结构的影响。方法:20周龄的雄性自发性高血压大鼠30只随机分为①Mox+SHR组;②Cap+SHR组;③SHR组, 每组10只。另设性别周龄相配的SD大鼠10只为正常对照组(NC组)。观察13周后处死动物, 获取心脏。测量左心室重/体重, 左室胶原分数, 标准化血管周胶原面积和肌间动脉中膜厚度的变化。结果:Mox+SHR组不仅左心室重/体重明显低于SHR组, 而且左室胶原分数低于SHR组(0.086±0.018vs0.046±0.015, P＜0.01), 血管外膜胶原少于SHR组(0.69±0.11vs1.34±0.29, P＜0.01), 中膜薄于SHR组。结论:盐酸莫索尼定长期抗高血压治疗能够减轻左室肥厚时的心肌纤维化和改善受损的冠脉微血管结构。     

苯那普利对高血压大鼠细胞外信号调节激酶和B型钠尿肽的影响

目的：研究苯那普利对自发性高血压大鼠（SHR）细胞外信号调节激酶（ERK）和B型钠尿肽（BNP）的影响。方法：选择Wistar Kyoto（WKY）大鼠作对照，将21只14周龄雄性SHR随机分成3组：未治疗组、肼苯哒嗪组和苯那普利组，每组7只。药物溶于载体（0.5%羧甲基纤维素钠）以灌胃法给予，肼苯哒嗪10 mg·kg-1·d-1，苯那普利10 mg·kg-1·d-1，SHR未治疗组及WKY组灌喂载体，共10周。以左心室重量与体重的比值反映心肌肥厚的程度；用袖带式尾动脉测压法测量大鼠尾动脉血压；分别用Western blotting方法和RT-PCR法半定量测定大鼠心肌中磷酸化ERK（p-ERK）的蛋白表达以及BNP mRNA的含量；酶联免疫吸附法检测大鼠血浆BNP水平。结果：（1） 治疗后SHR苯那普利组和SHR肼苯哒嗪组血压相似，均显著低于SHR未治疗组（P<0.01）。（2） SHR苯那普利组心肌肥厚指数显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.01) ，与WKY组无显著差异(P>0.05)；SHR肼苯哒嗪组和SHR未治疗组心肌肥厚指数无显著差异(P>0.05)。（3）SHR苯那普利组大鼠心肌p-ERK表达显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.05) ，与WKY组无显著差异(P>0.05)。SHR肼苯哒嗪组和SHR未治疗组大鼠心肌p-ERK表达无明显差异(P>0.05)。（4） SHR苯那普利组大鼠心肌BNP mRNA和血浆BNP水平显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.05)，与WKY组无显著差异(P>0.05)；SHR肼苯哒嗪组和SHR未治疗组大鼠心肌BNP mRNA和血浆BNP水平无明显差异(P>0.05)。结论：苯那普利能通过抑制ERK活性逆转心肌肥厚，伴随BNP水平下降；而降压效果相似的肼苯哒嗪不能抑制心肌肥厚，对p-ERK和BNP水平没有影响，提示BNP水平可以反映逆转心肌肥厚药物疗效。     

原发性高血压与应激性高血压大鼠NO/NOS、ET的变化

目的：探讨强物理因子诱发高血压后，一氧化氮（NO）／一氧化氮合酶（NOS）系统和内皮素（ET）的作用。方法：电击大鼠足底结合噪音刺激制作慢性应激性高血压大鼠（CSHR）模型，采用特异性放射免疫测定技术和化学比色法，检测原发性高血压大鼠（SHR）和正常血压（Wistar-kyoto WKY）大鼠，以及CSHR和正常血压Wistar大鼠心肌ET、NO和NOS的含量。结果：（1）SHR的尾动脉收缩压（CASP），左心室重量指数（LVW／BW）明显高于WKY大鼠（P〈0．01）。SHR的心肌ET水平明显高于WKY大鼠（P〈0．05）。（2）CSHR的CASP明显高于Wistar大鼠（P〈0．01），而LVW／BW及右心室重量指数（RVW／BW）与Wistar大鼠无差异（P〉0．05）。CSHR的心肌ET水平明显高Wistar大鼠（P〈0．01），而心肌NO及NOS水平则低于Wistar大鼠（P〈0．05）。结论：ET的增多以及NO／NOS系统功能低下可能参与了自发性高血压与慢性应激性高血压的发生和发展。NO／NOS系统和ET可能参与了SHR心肌肥厚的发生和发展。在CSHR中，应激四周可以造成血压升高，ET增多以及NO／NOS系统功能低下，但来发生心肌肥厚。     

Cellular distribution of calcium current is unaltered during compensated hypertrophy in the spontaneously hypertensive rat

Changes in cellular calcium (Ca²⁺) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca²⁺. The present study was performed to investigate whether changes in the distribution of I _Ca between the surface and t-tubule membranes might contribute to the altered Ca²⁺ handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I _Ca in the presence and absence of t-tubules. Membrane capacitance and I _Ca were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I _Ca both decreased and were no longer significantly different in the two cell types. The density of I _Ca was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I _Ca is unchanged in SHR myocytes compared to WKY controls; I _Ca density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I _Ca, so that the density of I _Ca at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca²⁺ release in the SHR at this stage of compensated hypertrophy.     

一氧化氮在压力超负荷心肌肥大作用中的定量分析

目的：探讨一气化氮（NO）在压力超负荷心肌肥大反应过程中的作用。方法：建立腹主动脉缩窄性高血压大鼠模型,测定平均动脉压（MAP）和左心室／体重比值（LVW／BW）;测量大鼠心肌的体积密度（Vv）、表面积密度（Sv）、比表面（S／V）及平均自由程（λ）等。结果：高血压大鼠的MAP、LVW／Bw、心肌横断面积、平均直径、Vv、Sv明显增大、入显著减小;加L-Arg组的MAP、LVW／BW值大致恢复至正常水平,心肌横断面积及平均直径、Vv、Sv等明显小于高血压组,S／V及入则增大;加L-NAME组的MAP、LVW／BW、心肌横断面积及平均直径、Vv、Sv等持续加大,而S／V及入则变小。结论：NO可明显改变体视学各项参数,对压力超负荷引起的高血压和心肌肥大具有明显的抑制作用。     

Structural adaptation of the rat left ventricle in response to changes in pressure and volume loads

Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used to explore the structural changes of cardiac dimensions in connection with a sustained hyperkinetic circulation, as induced by pregnancy or thyroxine administration. Cardiac design was assessed by recordings of the diastolic left ventricular pressure-volume relationships in isolated arrested hearts. Left ventricular weight: body weight and end-diastolic volume (EDV) for given end-diastolic pressures (EDP), were both increased about 50% in control SHR, with a marginal reduction of the wall:lumen ratio (w:ri) compared with control WKY. During the hyperkinetic circulatory states of pregnancy and hyperthyroidism, EDV was in WKY increased about 30% and 50%, respectively, with concomitant w:ri reductions. In SHR pregnancy did not significantly alter left ventricular dimensions, whereas EDV was increased by about 20% in hyperthyroid SHR. Thus, the rat left ventricle can, within 3 weeks, markedly alter not only the wall mass but also, and independently, the luminal design in response to different haemodynamic interventions. Early established SHR hypertension is characterized mainly by eccentric left ventricular hypertrophy, despite the elevated arterial pressure. Volume overloads in WKY due to pregnancy or hyperthyroidism can induce marked structural widening of the left ventricle. In SHR these structural luminal changes were only minor, perhaps because considerable eccentric hypertrophy is already present. Such a structural cardiac enlargement may allow delivery of an increased stroke volume for a given myocardial fibre shortening.     

不同年龄高血压大鼠心肌中MKP-1的表达及对心肌肥厚的影响

目的：研究不同年龄的自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）心室肌组织中丝裂原活化蛋白激酶（MAPK）及其磷酸酶（MKP-1）的表达以及与心肌肥厚的关系。方法： 用左心室重量与体重的比值作为心肌肥大指数并以此指标反映心肌肥厚；分别用Western blotting方法和RT-PCR法半定量测定心室肌组织中磷酸化细胞外信号调节激酶（p-ERK）的蛋白表达和MKP-1 mRNA的含量。结果： （1）SHR的血压自8周龄起明显高于WKY（P<0.01），心肌肥大指数明显大于WKY（P<0.05），ERK和MKP-1的表达均比WKY高（P<0.05）；（2）SHR的血压随年龄增长而升高（P<0.05），至14周趋于稳定，心肌肥大指数则在24周时出现激增（P<0.01）；（3）p-ERK随年龄增长呈递增趋势，而MKP-1呈递减趋势，且与心肌肥大指数和ERK的表达呈负相关（P<0.01）。结论： MKP-1在高血压大鼠随年龄和血压增加的心肌肥厚过程中起重要作用，其表达逐渐下降可能是导致ERK激活增加，进而引起心肌细胞肥大的重要原因。     

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats

In this study we investigated the effects of chronic β adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attentuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 ± 1.25; SHR-A = 56.72 ± 1.37) and subendocardium (SHR = 66.53 ± 1.27; SHR-A = 58.30 ± 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after β blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.     

The correlation of cardiac mass with arterial haemodynamics of resistive and capacitive load in rats with normotension and established hypertension

In hypertensive animals and humans, cardiac hypertrophy may occur as a consequence of an external load on the heart. Several studies have suggested that the non-pulsatile components of arterial haemodynamics, such as arterial pressure and vascular resistance, do not adequately represent the ventricular afterload and are not well correlated with the degree of cardiac hypertrophy (CH). The present study was undertaken to analyse the correlation between the degree of CH and various haemodynamic parameters in the spontaneously hypertensive rat (SHR) with established hypertension. A total of 36 SHRs (6–8 months) with a tail-cuff pressure above 190 mm Hg were used. Control data were obtained from 32 age-matched normotensive Wistar Kyoto rats (WKY). Animals were anaesthetized with pentobarbitone sodium (40 mg/kg i.p.) and artificially ventilated with a respirator. A Millar catheter with a high-fidelity pressure sensor was used to record the aortic pressure and an electromagnetic flow transducer to monitor the aortic flow. The pressure and flow signals were subjected to Fourier transformation for the analysis of the arterial impedance spectrum. The left ventricular weight-to-body weight ratio (LVW/BW) was taken as a measure of the degree of CH. The measured haemodynamic parameters in these anaesthetized, open-chest SHRs were systolic pressure (SP) (mean ± SE) 172±4 mm Hg, diastolic pressure (DP), 120±3 mm Hg, pulse pressure (PP) 52±2 mm Hg, peripheral resistance (R _p) 344,032±8,012 dyne · s · cm^–5, characteristic impedance (Z_c) 6,442±313 dyne · s · cm^–5, the impedance modulus at the first harmonic (Z1) 26,611±1,061 dyne · s · cm^–5, mean arterial compliance (C _m) 0.87 ±0.04 l/mm Hg and LVW/BW 3.092±0.026 mg/g. These parameters were significantly greater than the corresponding values in WKY, except that C _m was much decreased. In SHR, the LVW/BW was not significantly correlated with the SP, DP, R _p and steady external power. In contrast, the degree of CH was positively correlated with Z_c (r=0.66, P<0.001), Z1 (r=0.62, P<0.001) and pulsatile external work (r=0.41, P<0.05). It was also positively correlated with the backward pressure wave (r=0.42, P<0.05) and negatively correlated with C _m (r=-0.72, P<0.01). Such correlations of LVW/BW with pulsatile haemodynamics were not found in the normotensive WKY. The results indicate that the degree of cardiac hypertrophy in hypertensive rats, with a high blood pressure and increased stiffness of the arterial tree, is more closely related to pulsatile arterial haemodynamics than to the nonpulsatile components.     

Social stress, myocardial damage and arrhythmias in rats with cardiac hypertrophy.

In rat models of cardiac hypertrophy (moderate aortic coarctation: ACm, n=18; severe aortic coarctation: ACs, n=27; aging: OLD, n=25; spontaneous chronic hypertension: SHR, n=18) and properly matched control animals (C(ACm), n=17; C(ACs), n=19; C(OLD), n=24; C(SHR), n=22), we investigated the relative contribution of intense autonomic activity and cardiac structural damage to ventricular arrhythmogenesis. We used an "in vivo" to tissue level approach, by correlating in the same animal: (i) social stress-induced ventricular arrhythmias, telemetrically recorded, and (ii) left ventricular weights (LVW) and amount and geometrical properties of myocardial fibrosis (MF). Arterial blood pressure was significantly higher in ACm (+11%), ACs (+28%) and SHR (+34%) than in controls. LVW were approximately 20% greater in ACm, ACs and OLD and 50% greater in SHR. MF was about twice as great and characterized by more frequent occurrence of microscopic scarring in ACm and ACs, and eight times greater and associated with both a higher number and a larger size of fibrotic foci in OLD and SHR compared to controls. Social stress increased ventricular arrhythmia vulnerability in all models of cardiac hypertrophy, as well as in controls. The arrhythmogenic action of stress was facilitated in ACs, OLD and SHR. A correlation between structural cardiac remodeling and ventricular arrhythmias was found only in SHR and OLD, which exhibited the greatest increase in LVW and/or MF. Social stress proved to be a valuable tool for analyzing the combined effects of autonomic stimulation and altered myocardial substrate on the genesis of potentially life-threatening arrhythmias in social animals.     

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy.     

Left ventricular hypertrophy improves cardiac performance in spontaneously hypertensive rats

Cardiac function was studied in spontaneously breathing, adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY). By rapid intravenous blood infusion, the relation between left ventricular end-diastolic pressure (LVEDP) and stroke volume (SV) was determined while the cardiac nervous control was pharmacologically blocked. Since SV is greatly influenced by the level of afterload (mean arterial pressure, MAP), SV was also determined at increased MAP (constriction of abdominal aorta) and at decreased MAP (vasodilation by hydralazine). At low LVEDP levels, a righward shift of the Frank-Starling relationship was observed in SHR. This rightward shift seems mainly to depend on the increased MAP present in SHR since it was less prominent if MAP was lowered to normotensive levels in SHR. Maximal SV during volume infusion was similar in SHR and WKY, despite a much higher MAP in SHR. When peak SV was instead compared at similar MAP levels for both (either at ‘normotensive’ or ‘hypertensive’ levels) it was always significantly greater in SHR, and was increased largely in proportion to their increased left ventricular weight. This indicates that the left ventricular hypertrophy present in SHR is, at least at this stage, a physiological adaptation of the heart to increase its performance, in order to maintain a normal SV and hence cardiac output, despite an increased arterial pressure.     

Changes in myocardial capillary diffusion capacity during infusion of vasoactive drugs

The present study investigated how variations in coronary vascular resistance and metabolic demand affected myocardial capillary diffusion capacity. Hearts from Wistar rats were perfused with Krebs-Henseleit-albumin buffer in a Langendorff preparation, where heart rate (HR), contractility (dP/dt_max) and myocardial oxygen consumption (MVO₂) were recorded continuously. Myocardial capillary diffusion capacity was measured as the permeability surface area product (PS) for Cr-EDTA and vitamin B₁₂ by the single injection colorimetric indicator dilution method. After base-line recordings without drugs, angiotensin II + arginine-vasopressin was infused, which increased coronary vascular resistance by 90%, stimulated HR by 11%, decreased dP/dt_max by 21% and reduced MVO₂ by 4%. PS_Cr-EDTA and PS_B12, decreased by 24 and 27%, respectively, leaving the ratio PS_Cr-EDTA/PS_B12 unchanged indicating unaltered capillary permeability. Moreover, the reductions in MVO₂ and PS correlated significantly. During vasodilation: (1) nitroprusside-NA stimulated HR by 7% and decreased dP/dt_max by 14%; (2) adenosine reduced dP/dt_max by 37% and decreased MVO₂ by 9%; and (3) isoproterenol increased HR, dP/dt_max and MVO₂ by 53, 76 and 9%, respectively. However, all three vasodilators reduced PS_Cr-EDTA and PS_B12 in parallel by 7–25% leaving PS_Cr-EDTA/PS_B12 unchanged. Thus, maximal estimated diffusion capacities were obtained during spontaneous coronary vascular tone, most likely reflecting maximal capillary recruitment in the Krebs-Henseleit-albumin perfused heart. The derecruiting effects of the vasoconstrictors were partly overridden by metabolic factors, while the reductions of PS after vasodilation more likely were due to increased heterogeneity in coronary flow.     

Effects of exercise training on pathological cardiac hypertrophy related gene expression and apoptosis

This study determined whether exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial and apoptosis-associated genes. We used spontaneously hypertensive rats (n=15, non-exercise SHR), exercise-trained SHR (n=15, treadmill exercise for 12 weeks), and sedentary Wistar-Kyoto (WKY) rats (n=15). Exercise-trained SHR expressed adaptive changes such as reduced body weight, heart rate, blood pressures, left ventricle wall thickness, lipid profiles, and homocysteine level. The mRNA expression of angiotensin converting enzyme, endothelin-1, and brain natriuretic peptides in the heart was lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR, whereas mRNA expression of caveolin-3 and eNOS in the heart was higher. Bcl-2 protein was higher in the exercise-trained SHR than in the WKY and the non-exercise SHR. In contrast, Bax protein levels were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. Furthermore, the levels of the active forms of caspase-3 (20 kDa) were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. These findings suggest that exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial genes and that it interferes with a signal transduction pathway of apoptosis secondary to the pathological cardiac hypertrophy.     

Arterial haemodynamics on ventricular hypertrophy in rats with simulated aortic stiffness

Aortic stiffness (AS) exerts significant impact on the cardiovascular risks. We developed a new model to produce AS. The purposes were to evaluate the haemodynamic consequence and to correlate the haemodynamic parameters with the extent of ventricular hypertrophy (VH). We applied silicon gel for embedding of the abdominal and/or thoracic aorta. After 1–4 weeks of AS, the left ventricular weight (LVW), LVW to body weight (BW) ratio (LVW/BW), and the morphological changes in cardiomyotes were quantified for VH. We determined the aortic pressure (AP), stroke volume, cardiac output, total peripheral resistance (TPR), characteristic impedance (Zc), pulse wave reflection (P_b) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, P_b and PWV accompanied by decreases in diastolic pressure and arterial compliance. The magnitude of these haemodynamic and cardiac changes were in an order of combined, thoracic and abdominal AE. Correlation analysis revealed that the VH was well correlated with pulsatile haemodynamics such as Zc, PP, P_b and PWV, while less with steady components (Mean AP and TPR). Our results indicate that pulsatile haemodynamic parameters are significantly elevated after AS. The alterations in pulsatile haemodynamics are the major causes leading to VH.     

Cardiac function and morphology with aging in the spontaneously hypertensive rat.

To determine the effects of a chronic pressure load on cardiac function and morphology, spontaneously hypertensive rats (SHR) and two normotensive strains of Wistar rats (WKY and NWR) were studied under ether anesthesia at 13, 25, 52, and 90 wk of age. Although resting cardiac index of the SHR was comparable to that of WKY and NWR at all ages, the peak cardiac output and peak stroke volume per gram of left ventricle determined during a rapid intravenous infusion of Tyrode solution was markedly reduced in the SHR only at 90 wk of age. Autonomic inhibition did not alter the peak stroke volume attained, but reduced peak cardiac output at all ages in each of the strains. Absolute left ventricular dimensions in the SHR increased out of proportion to body growth, consistent with concentric hypertrophy. As peak pumping ability markedly declined from 52 to 90 wk of age in the SHR, the free wall of the left ventricle greatly thickened whereas the septum remained unchanged. At this time the right ventricle also hypertrophied. This disproportionate thickening of the walls of the left ventricle and the hypertrophy of the right ventricle were reflected in measurements of their fiber diameters. These alterations in ventricular architecture may contribute to the decrease in pumping ability observed in long-standing hypertension.     

Zona reticularis in aging spontaneously hypertensive rats: a quantitative ultrastructural study of 70- and 95-week-old animals.

The zona reticularis of 70- and 95-week-old female Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats was studied by quantitative stereologic techniques. The zona reticularis in the adrenal gland of 70-week-old SH rats was virtually identical to that of 70-week-old WKY rats. In both SH and WKY rats at 95 weeks of age, however, there was hypertrophy of smooth endoplasmic reticulum reflected quantitatively in increased volume and surface area, as compared with that of WKY rats or SH rats at 70 weeks of age. Ninety-five-week-old WKY rats had a significantly greater mitochondrial volume/cell and surface area of mitochondrial membranes than SH rats. Inclusion of lipid droplets within mitochondria was seen in zona reticularis cells from SH and WKY rats at 70 weeks of age; mitochondria-lipid-droplet association was more frequent at 95 weeks of age. The volume of lipofuscin per cell was significantly greater in WKY than in SH rats at 95 weeks of age. Thus, by quantitative techniques, one can see that the zona reticularis of 95-week-old SH rats differs from that of WKY rats, principally in the presence of smaller cells with a smaller surface area of mitochondrial cristae and a reduced volume of mitochondria, lipofuscin, and lipid droplets.