5-羟色胺对去甲肾上腺素诱导大鼠心肌肥厚的影响

目的　了解 5 羟色胺 (5 HT)对去甲肾上腺素(NE)所致心肌肥厚有何影响。方法　大鼠分别ip5 HT 2mg·kg- 1,NE 2mg·kg- 1或NE 2mg·kg- 1+ 5 HT 2mg·kg- 1。每日 2次 ,连续给药 15d ,d 16麻醉 ,颈动脉插管 ,观察累积iv不同剂量 5 HT对平均动脉压和心电图的影响 ,之后处死大鼠 ,观察心重与体重之比。结果　累积iv 5 HT ,NE组和NE + 5 HT组大鼠血压明显升高 ,诱发室速和室颤的鼠数明显增加 ,但该两组间无显著差异。NE组心室重与体重之比明显增加 ,NE + 5 HT组较NE组相比进一步增加。结论　 5 HT加强NE诱发大鼠心肌肥厚和心律失常的作用。     

维药异叶青兰总黄酮对去甲肾上腺素诱导的大鼠心肌细胞肥大的影响

目的研究维药异叶青兰总黄酮(TFDH)对去甲肾上腺素(NE)诱导的心肌细胞肥大的作用,并探讨其作用机制。方法以原代培养的新生大鼠心肌细胞与TFDH 10,25和50μmol·L~(-1)孵育30 min后,加入NE 2μmol·L~(-1)共培养48 h。CCK-8法观察心肌细胞存活率;RT-PCR法检测心肌肥大基因心房利钠肽(ANP)和β-肌球蛋白重链(β-MHC)的m RNA表达水平;激光共聚焦法检测心肌细胞的表面积和细胞内钙离子浓度([Ca~(2+)]_i);破碎细胞后酶促反应测定Ca~(2+)-ATP酶的活性;比色法测定一氧化氮(NO)浓度和一氧化氮合酶(NOS)活性。结果与细胞对照组相比,NE 2μmol·L~(-1)刺激心肌细胞48 h,可使心肌细胞相对存活率由细胞对照组的(95±1)%下降至(78±5)%(P<0.05);细胞表面积由(178±29)μm~2显著增加至(274±38)μm~2(P<0.05);ANP和β-MHC m RNA相对表达水平显著上调,分别由细胞对照组的1.00±0.01和1.00±0.02升高至2.76±0.55和2.69±0.31(P<0.05);心肌细胞内[Ca~(2+)]_i显著升高,由细胞对照组的(1.00±0.12)升高至(1.52±0.41)μmol·L~(-1),Ca~(2+)-ATP酶的活性显著下调,由细胞对照组的(1.01±0.14)下降至(0.41±0.06)μmol·L~(-1)(P<0.05);NO浓度由细胞对照组的(1.50±0.14)下降至(1.12±0.05)μmol·L~(-1),NOS活性由细胞对照组的(0.86±0.06)下降至(0.52±0.10)μmol·L~(-1)(P<0.05)。给予TFDH 10~50μmol·L~(-1)能对抗NE引起的心肌细胞存活率下降和表面积增大,对NE引起的ANP和β-MHC m RNA表达增加也有一定抑制作用(P<0.05),同时对心肌细胞内[Ca~(2+)]_i升高、Ca~(2+)-ATP酶活性下降及NO浓度和NOS活性下降也具有一定的对抗作用(P<0.05)。结论TFDH能改善NE诱导的心肌细胞肥大,提高心肌细胞存活率,下调ANP和β-MHC m RNA的表达,减小心肌细胞表面积,其机制可能与促进NO释放、调节细胞内Ca~(2+)浓度和a~(2+)-ATP酶活性有关。     

Transgenerational left ventricular hypertrophy and hypertension in offspring after uteroplacental insufficiency in male rats

Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar‐Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months‐of‐age, F1 and F2 restricted offspring had elevated blood pressure (8–15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.     

Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats

Context: Hydroxysafflor yellow A (HSYA), the main chemical component of the safflower yellow pigments, is used extensively in traditional Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.

Objective: The present study determined the effects of HSYA on left ventricular hypertrophy after pressure overload and investigated the underlying mechanisms.

Materials and methods: Cardiac hypertrophy was induced by the ligation of abdominal aorta in male Wistar rats. The rats were then divided into five groups and treated with captopril (100?mg/kg) or HSYA at different doses (0, 10, 20 and 40?mg/kg). Six weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions of Bcl-2 and Bax were evaluated by immunohistochemistry.

Results: HSYA (20, 40?mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body weight) by 13.04 and 30.43% respectively, when compared with the model group. This was associated with the amelioration of pathological lesion, such as cardiac muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained in animals treated with HSYA (20, 40?mg/kg). In addition, the administration of HSYA at doses of 20 and 40?mg/kg increased the Bcl-2/Bax ratio (1.17?±?0.08 and 1.39?±?0.07 versus 0.71?±?0.06). In addition, the serum MMP-2 and MMP-9 levels were blocked by the treatment at doses of 20 and 40?mg/kg HSYA (MMP-2, 76.1?±?9.2 and 65.6?±?6.8 versus 82.9?±?6.2, ng/ml; MMP-9, 66.6?±?4.8 and 57.5?±?5.0 versus 83.5?±?6.0, ng/ml).

Conclusion: These findings indicated that HSYA has beneficial effects on hypertensive ventricular remodeling, which may involve mechanisms of inhibiting cell apoptosis and suppressing metalloproteinases expression.     

Resveratrol inhibits right ventricular hypertrophy induced by monocrotaline in rats

1. Resveratrol (RSV), a polyphenol in red wine, exhibits cardioprotective effects in vitro, such as inhibition of angiotensin II‐ or phenylephrine‐induced cardiomyocyte hypertrophy in rat neonatal myocyte cultures and suppression of cardiac fibroblast proliferation. The aim of the present study was to investigate the protective effects of RSV against monocrotaline (MCT)‐induced right ventricular (RV) hypertrophy in rats. 2. Male Sprague‐Dawley rats were given a single injection of MCT (50 mg/kg, s.c.) and were then treated with either vehicle (normal saline) or RSV (10 and 30 mg/kg, i.g., twice daily) for 21 days. A separate group of control rats were not injected with MCT and were treated with normal saline for 21 days. At the end of the treatment period, all rats were subjected to echocardiography and haemodynamic measurements. In addition, after rats had been killed, the hearts were subjected to histopathological, untrastructural and immunohistochemical analyses. 3. In vehicle‐treated rats, MCT injection resulted in 33% mortality, whereas mortality in RSV‐treated MCT‐injected rats was 0%. In vehicle‐treated rats, MCT increased RV free wall thickness and RV systolic pressure and decreased pulmonary arterial acceleration time at the end of the experimental period. These dynamic changes were ameliorated by RSV in a dose‐dependent manner. Histologically, MCT injection resulted in RV hypertrophy, swollen mitochrondria and cardiomyocyte apoptosis; all these morphological changes were dose‐dependently improved in rats treated with RSV. 4. In conclusion, RSV inhibits the RV hypertrophy induced by MCT in rats and this effect is mediated by both a direct effect of RSV on cardiomyocytes and an indirect effect mediated via a reduction in pulmonary hypertension.     

Inotropic responses to phosphodiesterase inhibitors in cardiac hypertrophy in rats

In the present study we sought to determine whether reduced contractile responses to phosphodiesterase inhibitors occur in the face of chronic cardiac hypertrophy associated with beta-adrenergic inotropic downregulation. As compared to age-matched Wistar-Kyoto control rats, spontaneously hypertensive rats at 6-8 months of age exhibited a striking decrease in left ventricular inotropic responses induced by isoproterenol, a beta-adrenoceptor agonist, in isolated, isovolumically contracting heart preparations. Despite profound beta-adrenoceptor-mediated inotropic downregulation, similar contractile responses to the phosphodiesterase III selective inhibitors, amrinone and milrinone, the phosphodiesterase IV selective inhibitor, rolipram, and non-selective phosphodiesterase inhibitor, pentoxifylline, were detected in normal and hypertrophic heart preparations. Moreover, the inotropic potency of the cAMP analogue, 8-Br-cAMP, was increased in spontaneously hypertensive rats. These findings suggest that in chronic cardiac hypertrophy, contractile responses to phosphodiesterase inhibitors may be preserved despite marked reductions in inotropic responses to beta-adrenoceptor agonists.     

Effect of spirapril on left ventricular hypertrophy due to volume overload in rats.

The effect of the angiotensin-converting enzyme (ACE) inhibitor spirapril on structural and functional parameters of volume-overloaded rat hearts was evaluated in a time-course study. Left ventricular hypertrophy (LVH) was induced by graded disruption of the aortic valve in male Wistar rats. Four weeks later, structural (LV mass and LV wall thickness) as well as functional parameters [LV end-systolic and end-diastolic volumes, stroke volume (SV), ejection fraction (EF)] were determined in anesthetized animals by magnetic resonance imaging (MRI). The rats were then divided into two groups, one of them receiving spirapril (10 mg/kg/day) in food. LV parameters were evaluated by MRI at 4, 18, 25, and 32 days after treatment was started. MRI analysis before the start of treatment showed that both groups had developed a similar degree of eccentric LV hypertrophy. Similarly, LV wall thickness, end-systolic and end-diastolic volumes, SV, and EF did not differ between the groups. Treatment with spirapril resulted in stable LV weight during the follow-up period of 32 days, whereas the untreated group showed a significant steady increase in heart weight. LV end-diastolic volume, LV end-systolic volume, and SV were smaller in the spirapril group when measured after 25 and 32 days, but only the difference in end-diastolic volume reached statistical significance. LV wall thickness and EF were not affected by spirapril. After the last MRI determinations, blood pressure (BP) and the response to angiotensin I (ANGI) were measured in conscious animals. Systolic BP (SBP) and mean arterial pressure (MAP) were significantly lower in spirapril-treated rats, and the dose-response curve to ANGI was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac and vascular responses in deoxycorticosterone acetate-salt hypertensive rats

1. Hypertension leads to ventricular hypertrophy and, eventually, to heart failure. The present study has investigated the functional consequences of deoxycorticosterone acetate (DOCA)-salt hypertension in rats by defining the inotropic, chronotropic and vascular responses to noradrenaline (NA; beta1-adrenoceptor agonist), forskolin (adenylate cyclase activator) and theophylline (phosphodiesterase inhibitor). 2. Administration of DOCA (25 mg, s.c., every 4th day) and excess salt (1% NaCl in drinking water) to uninephrectomized rats increased left ventricular wet weight by 35 and 71% after 4 and 8 weeks, respectively. Addition of KCl (0.4%) or CaCl2 (1%) in the drinking water for 4 weeks attenuated blood pressure increases, but not ventricular weight increases (46 and 28%, respectively). 3. Positive inotropic responses in papillary muscles from uninephrectomized rats to NA (-log EC50 6.73+/-0.38; n = 7), forskolin (-log EC50 6.15+/-0.31; n = 7) and CaCl2 (-log EC50 2.40+/-0.02; n = 14) were unchanged in hypertrophied left ventricles of DOCA and DOCA-CaCl2 rats, although maximal responses to NA were decreased in DOCA-KCI rats (1.2+/-0.6 mN, n = 8; DOCA-salt 2.9+/-0.5 mN, n = 6); theophylline was less potent in DOCA-salt rats. Positive chronotropic responses to NA, forskolin and theophylline in right atria and negative inotropic responses to carbachol in papillary muscles were unchanged. 4. Maximal vasoconstrictor responses to NA in thoracic aortic rings were reduced in DOCA-KCI rats to 2.4+/-0.9 mN (n = 5), but were increased in DOCA-CaCl2 rats to 26.6+/-2.2 mN (n = 7; DOCA-salt 7.8+/-2.2 mN, n = 9). Vasorelaxant responses to forskolin and theophylline were unchanged. 5. These results show that cardiac responses are only minimally affected during the development of DOCA-salt hypertension-induced hypertrophy, despite the reported decreases in adenylate cyclase activity, in these rats. This is in contrast with the decreased responses reported in other rat models of cardiac hypertrophy and in the failing human heart. Thus, hypertrophy in hearts of DOCA-salt hypertensive rats does not produce similar changes to the failing human heart.     

牛磺酸对肾血管性高血压大鼠左室肥厚的保护作用

目的　观察牛磺酸 (Tau)对肾血管性高血压大鼠左室肥厚的影响 ,并探讨其机制。方法　建立二肾一夹 (2K1C)肾动脉狭窄性高血压模型。羟脯氨酸法测定大鼠心肌胶原含量 (MCC) ;放免法测定心肌AngⅡ (MAC)及Ald(MDC) ;原位杂交方法检测c fosmRNA表达 ;显微镜观察心肌组织结构改变并测量心肌纤维直径 (MFD) ,并进行线性相关分析。结果　 2K1C组大鼠MCC、MAC、MDC含量及MFD较Sham组增加 (P <0 0 1) ,c fosmRNA表达高于Sham组 (P<0 0 1) ;心肌冠状动脉周围胶原纤维大量增生并向周围间质延伸 ;相关分析显示MCC及MFD皆与MAC、MDC正相关 (P <0 0 1)。牛磺酸 (5 0mg·kg-1·d-1)治疗 8wk降低2K1C大鼠尾动脉收缩压 (SBP)、MAC、MDF及MCC(P <0 0 1) ,左心室 /体重比 (LVWI)、MDC及心室肌c fosmRNA表达量亦明显下降 (P <0 0 1) ,并抑制心肌冠脉周围胶原纤维增生。结论　牛磺酸可通过降低心肌局部RAAS活性及c fosmRNA表达 ,从而抑制心肌细胞肥大及胶原纤维增生 ,有效防治肾血管性高血压左室肥厚。     

Effects of indapamide in rats with pressure overload left ventricular hypertrophy

We studied the in vivo effects of the antihypertensive diuretic agent indapamide on left ventricular (LV) morphology in chronically pressure-overloaded rat hearts. LV pressure and subsequently LV mass were increased by banding the ascending aorta over a period of 6 weeks. Thereafter, animals were treated with low-dose (1 mg/kg/day, n = 9) or high-dose (10 mg/kg/day, n = 9) indapamide for another 6 weeks. Low-dose indapamide treatment reduced LV weights as compared with vehicle-treated controls (n = 9; -12%; p = 0.008). Furthermore, low-dose indapamide treatment resulted in a decrease of myocyte volume (59.0 +/- 10.6 vs. 79.0 +/- 9.8 m3 x 10(-27); p < 0.05) and an improvement of molecular markers of hypertrophy: a reduction of LV atrial natriuretic factor mRNA expression (-37%; p < 0.05), and an increase of the V1/V3 myosin ratio (+121%; p < 0.05). Low-dose indapamide also reduced significantly plasma (-65%) and LV angiotensin-converting enzyme (ACE) activities (-74%) as well as LV mRNA levels (-24%). These changes were observed despite continued pressure overload of the LV and despite a lack of significant changes in sodium excretion with the prolonged administration of low-dose indapamide. High-dose indapamide treatment showed no significant effects on LV mass, structure, and gene expression. Furthermore, high-dose indapamide increased plasma renin activity substantially, whereas low-dose treatment was without effect on circulating renin. In conclusion, in rats with continuous LV pressure-overload low-dose treatment with indapamide leads to mild regression of cardiac hypertrophy, accompanied by a downregulation of components of the cardiac renin-angiotensin system. These effects may be mediated by mechanisms apart from the known diuretic and antihypertensive actions of indapamide, because sodium excretion and blood pressure were stable with long-term treatment and are unlikely to be related to LVH regression in this model.     

辛伐他汀对主动脉狭窄大鼠左心室肥大和功能的影响

AIM: To investigate the effects of simvastatin (Sim) on left ventricular hypertrophy in rats with pressure-overload cardiac hypertrophy. METHODS: The left ventricular hypertrophy (LVH) of rats was induced by partly occluding abdominal aorta below right renal artery. The rats were given i.g. Sim (1.8 and 3.6 mg.kg-1.d-1) for 8 wk. Three days after operation, left ventricular function was measured. Then the left ventricle (LV) + septum and the right ventricle (RV) were weighed. Hydroxyproline content of LV was measured. RESULTS: Eight weeks later, in the LVH group, LV weight (LVW), LVW/body weight (BW), LVW/RV weight (RVW), LV ending diastolic pressure (LVEDP), and hydroxyproline content increased by 36%, 51%, 28%, 92%, and 23%, respectively (all P < 0.01) compared with the sham group. LV + dp/dtmax and -dp/dtmax decreased by 39.2% and 39.4% (all P < 0.01). After the rats were given i.g. Sim 3.6 mg.kg-1.d-1, LVW, LVW/BW, LVW/RVW, left ventricle ending diastolic pressure (LVEDP), and hydroxyproline content decreased by 22%, 21%, 23%, 24%, and 11% compared with LVH group (all P < 0.01), LV + dp/dtmax and -dp/dtmax increased by 60% and 32% (all P < 0.01). CONCLUSION: Sim inhibited development of LV hypertrophy and improved LV function in rats with aortic stenosis.     

Influence of ramipril on right ventricular hypertrophy induced by pulmonary artery stenosis in rats.

The influence of the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg orally in a single daily dose) on right ventricular (RV) hypertrophy was studied in Sprague Dawley rats. The pulmonary artery was banded to an outer diameter of 1.7 mm. After 14 days, left (LV) and RV hemodynamic parameters were measured in anesthetized animals. Furthermore, regional heart weights were determined, and myocytes of three different heart regions were isolated and subjected to morphometric analysis. Pulmonary artery stenosis caused a marked increase in RV systolic blood pressure (SBP) without alteration of LV functional parameters as compared with sham-operated animals. Correspondingly, the weight of the RV free wall as well as the RV cell volume were increased to about the same extent, while the LV weight was unchanged. Administration of ramipril to pulmonary artery-constricted animals slightly reduced LV SBP and LVdP/dtmax as compared with banded animals without treatment. The increase in RV SBP and the weight gain of the RV free wall were not affected, however. In contrast, the increase in cell volume of isolated myocytes was less pronounced in this group (+27% as compared with +58% in untreated animals). Because there were no differences in water content of the tissue, interstitial or cellular edema cannot be responsible for this discrepancy. Thus, ACE inhibition with ramipril appears to blunt the cellular hypertrophy in this model without affecting the weight gain of the RV.     

Total ginsenosides inhibit the right ventricular hypertrophy induced by monocrotaline in rats

Ginsenosides have been reported to release nitric oxide (NO) and decrease intracellular free Ca(2+) in cardiovascular system, which play important roles in antihypertrophic effect. This study investigated the potential inhibitory effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT, 60 mg/kg/d) and examined the possible antihypertrophic mechanism in male Sprague Dawley rats. MCT-intoxicated animals were treated with TG (20, 40, 60 mg/kg/d) for 18 d. TG treatment ameliorated MCT-induced elevations in right ventricular peak systolic pressure, right ventricular hypertrophy and the expression of atrial natriuretic peptide; N(G)-nitro-L-arginine-methyl ester (L-NAME), an NO synthase (NOS) inhibitor, had no influence on these inhibitory effects of TG 40 mg/kg/d, and TG at this dose had no any effect on the eNOS mRNA expression, suggesting the limited rule of NO in TG's effects. To further examine the mechanisms of the protection, the expression of calcineurin and its catalytic subunit CnA, as well as extracellular signal-regulated kinase-1 (ERK-1) and mitogen-activated protein kinase (MAPK) Phosphatase-1 (MKP-1) was examined. TG treatment significantly suppressed MCT-induced elevations of these signaling pathways in a dose-dependent manner. In summary, TG is effective in protecting against MCT-induced right ventricle hypertrophy, possibly through lowering pulmonary hypertension. Multiple molecular mechanisms appeared to be involved in this protection, such as the suppression of MCT-activated calcineurin and ERK signaling pathways.     

辛伐他汀对野百合碱所致大鼠右心室肥大的抑制作用

目的 :观察辛伐他汀 (Sim)抑制大鼠右心室肥大的作用。方法 :一次性皮下注射野百合碱 (MCT) 5 0mg·kg-1 ,引起大鼠肺动脉高压和右心室肥大。 2周后 ,分组灌胃给予Sim 1 .5 ,3.0mg·kg-1 ·d-1 或纯化水 (对照组 ) ,连续治疗 1 4d。测定各组大鼠的平均肺动脉压、右心室和左心室 室间隔的重量比 [R/(L S) ]、右心室组织的蛋白和羟脯氨酸含量 ,并观察右心室和肺的病理形态。结果 :Sim 3.0mg·kg-1 ·d-1 给药 1 4d ,使R/(L S)、蛋白质和羟脯氨酸含量分别比对照组大鼠减少 35 %,6 2 %,38%(P <0 .0 1 )。但对MCT引起的大鼠肺动脉压升高和肺组织形态改变无影响。结论 :Sim对MCT引起的大鼠右心室肥大的进程具有抑制作用。     

5—羟色胺增强去甲肾上腺素诱导的肥厚心肌L—型钙电流

目的:研究5-羟色胺(5-HT)对去甲肾上腺素(NE)诱导的大鼠肥厚心肌L-型钙电流(I_(Ca))的影响.方法:大鼠腹腔注射NE建立心肌肥厚模型;酶解分离单个心室肌细胞;全细胞膜片箝记录I_(Ca).结果:(1)腹腔注射NE第15天,大鼠左心室与体重比增加31.8％(2)肥厚心肌细胞I_(Ca)与正常心肌细胞相比,明显增加0mV时分别为4.5pA/pF±0.5pA/pF和3.5pA/pF±0.3pA/pF(P<0.01).(3)5-HT可显著增加肥厚和正常心肌细胞I_(Ca),并使最大激活电流从0mV降低至-10mV;此外,5-HT增加I_(Ca)作用在肥厚心肌细胞更为显著.(4)稳态激活和失活实验发现,5-HT对稳态激活曲线无显著影响,而影响稳态失活曲线,使半失活电压从-39.5mV±1.8mV升高至-27.8mV±1.7mV(P<0.05),而不改变钙通道电压依赖性(斜率因子k无显著变化).结论:5-HT通过改变L-型钙通道稳态失活特征而显著增加I_(Ca),此作用在肥厚心肌细胞更显著,提示在肥厚心肌5-HT更易于诱导心律失常发生.     

The neutral endopeptidase inhibitor, SCH 34826, reduces left ventricular hypertrophy in spontaneously hypertensive rats.

SCH 34826, i.e., (S)-N-(N-(2,2[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]-2-oxo-1-(phenyl-methyl)ethyl)-phenylalanyl)-beta-alanine, is a potent and selective inhibitor of neutral endopeptidase 24.11 (NEP), an enzyme that degrades the atrial natriuretic peptide (ANP). The effects of SCH 34826 on hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) were evaluated following 1 month of treatment by measuring the blood pressure, cardiac weight, and left ventricular fibrosis. Adult SHRs were treated with SCH 34826 at 10, 30, or 100 mg/kg given orally twice daily or with vehicle. The systolic blood pressure (SBP) and heart rate (HR) were recorded weekly by the tail-cuff method. Cardiac structural damage was determined by morphometric analysis. Over the dose range examined, the drug produced no significant changes in either blood pressure or heart rate. Despite the lack of antihypertensive activity, SCH 34826 at 100 mg/kg reduced both the cardiac mass (-10%) and the amount of fibrotic tissue present in the left ventricle (-42%). These data indicate that chronic inhibition of NEP by SCH 34826 interacts with mechanisms underlying myocardial hypertrophy and cardiac remodeling.     

The angiotensin type 1 receptor antagonist valsartan attenuates pathological ventricular hypertrophy induced by hyperhomocysteinemia in rats.

INTRODUCTION: Clinical and experimental studies have reported the role of homocysteine in ventricular hypertrophy. Activation of the renin-angiotensin system mediated by angiotensin II type 1 (AT1) receptor has also been suggested to contribute to the pathogenesis of ventricular hypertrophy. There are also reports suggesting the affect of angiotensin II (Ang II) on cardiac hypertrophy is mediated by hyperhomocysteinemia. However, there is limited information on the mechanisms of the possible relationship between homocysteine and Ang II in ventricular hypertrophy. In this study we tested the hypothesis that hyperhomocysteinemia induced ventricular hypertrophy and remodelling may be mediated through activation of Ang II AT1-receptors in rats. METHODS: This study was conducted on control non-treated rats (n=13), methionine-treated rats (1.5 mg/kg/day, n=18) and methionine plus oral AT1 antagonist (valsartan, 30 mg/kg/day, n=13) treated rats for 56 days. Systolic blood pressure (SBP) was determined in rats at baseline, 28 and 56 days. Echocardiography was also performed in all rats after eight weeks, and blood samples were obtained for determination of plasma tHcy. Rats were then sacrificed for histopathological and biochemical assessment of cardiac structure. RESULTS: The SBP in the methionine-treated rats was significantly higher compared with controls and significantly lower compared with the methionine-valsartan group at 28 and 56 days (p<0.001). In addition, left ventricular wall thickness (LVWT) in the methionine-valsartan group (4.36+0.11 mm) was significantly lower compared with the methionine group (5.0+0.23 mm, p=0.03). Furthermore, cardiac collagen to total protein ratio was significantly lower in the methionine-valsartan group (2.19+0.11%) compared with the methionine group (2.64+0.08%, p=0.026). Fractional shortening (FS) was not significantly different between groups. CONCLUSION: Results from this study suggest that hyperhomocysteinemia-induced hypertension and ventricular hypertrophy in rats are mediated, at least partly; by Ang II activation of AT1-receptors.     

粉防己碱逆转肾血管性高血压大鼠左心室肥厚并改善心功能

为观察粉防己碱对肾血管性高血压大鼠的心肌肥厚逆转作用以及对其离体工作心脏心功能和血流动力学情况的改善作用，采用二肾一夹肾型高血压形成大鼠左心室肥厚结果表明粉防己碱50 mg·kg^-1·d^-1 ig，治疗8周时，肾血管性高血压大鼠血压降至正常，其左心室湿重/体重指数较肥厚组降低22.5%; 在离体工作心脏，粉防己碱组心脏的舒张和收缩功能及心脏泵功能均明显改善，接近正常水平.结果说明粉防己碱对高肾素型高血压所致的左心室肥厚具有逆转作用，同时明显改善心脏的舒张收缩功能和血流动力学.     

Salubrinal attenuates right ventricular hypertrophy and dysfunction in hypoxic pulmonary hypertension of rats

The phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α) is essential for cell survival during hypoxia. The aim of this study was to investigate whether salubrinal, an inhibitor of p-eIF2α dephosphorylation could attenuate pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy in rats exposed to hypobaric hypoxia. PAH of rats was induced by hypobaric hypoxia. Salubrinal supplemented was randomized in either a prevention or a reversal protocol. At the end of the follow-up point, we measured echocardiography, hemodynamics, hematoxylin-eosin and Masson's trichrome stainings. RNA-seq analysis is explored to identify changes in gene expression associated with hypobaric hypoxia with or without salubrinal. Compared with vehicle-treatment rats exposed to hypobaric hypoxia, salubrinal prevented and partly reversed the increase of the mean pulmonary artery pressure and RV hypertrophy. What's more, salubrinal reduced the percentage wall thickness (WT%) of pulmonary artery and RV collagen volume fraction (CVF) in both prevention and reversal protocols. We also found that salubrinal was capable of reducing endoplasmic reticulum stress and oxidative stress. The result of RNA-seq analysis revealed that chronic hypoxia stimulated the differential expression of a series of genes involved in cell cycle regulation and ventricular hypertrophy and so on. Some of these genes could be ameliorated by salubrinal. These results indicate that salubrinal could prevent and reverse well-established RV remodeling, and restore the genes and pathways altered in the right ventricles of rats exposed to hypobaric hypoxia.