Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats

OBJECTIVES: To elucidate the relationship between renin-angiotensin system and nitric oxide in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, angiotensin-converting enzyme inhibitor, on endothelial-cell nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in the left ventricle (LV) and its relation to myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. METHODS: In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of fatal left ventricular failure with chamber dilatation at 18 weeks (DSCHF). Imidapril (DSCHF-I, n = 7, 1 mg/kg/day, subdepressor dose) or vehicle (DSCHF-V, n = 7) were given from DSLVH to DSCHF stage for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet were served as control group (DR-C, n = 7). RESULTS: Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSCHF-V was significantly ameliorated in DSCHF-I using transthoracic echocardiography. The level of eNOS mRNA and protein in the LV was significantly suppressed in DSCHF-V compared with DR-C, and significantly increased in DSCHF-I compared with DR-C and DSCHF-V. The iNOS mRNA and protein and the fibrosis factor expression of type I collagen mRNA were significantly increased in DSCHF-V compared with DR-C, and significantly decreased in DSCHF-I compared with DSCHF-V. DSCHF-V demonstrated a significant increase in wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These changes in the microvasculature were improved significantly by imidapril. CONCLUSIONS: Subdepressor dose of imidapril may ameliorate the endothelial damage not only by inhibiting production of angiotensin II but also by promoting eNOS and inhibiting iNOS mRNA and protein expression in the LV, and this increased eNOS mRNA and protein level may have a role in the improvement of congestive heart failure and myocardial remodelling.     

Effects of imidapril on endothelin-1 and ACE gene expression in failing hearts of salt-sensitive hypertensive rats

The renin-angiotensin system and endothelin are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) is reported in patients with heart failure, the detailed mechanism remains to be determined. To elucidate the relationship between the renin-angiotensin system and ET-1 in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, an angiotensin converting enzyme (ACE) inhibitor, on preproET-1, endothelin A receptor (ETAR), and ACE mRNA expression in the left ventricle and evaluated these in relation to myocardial remodeling in the failing heart of Dahl salt-sensitive (DS) hypertensive rats fed a high salt diet. In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of left ventricular failure with chamber dilatation at 18 weeks (DSHF). Imidapril (DSHF-IM, n = 8, 1 mg/kg/day, subdepressor dose) or vehicle (DSHF-V, n = 8) was given from stage DSLVH to DSHF for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet served as the control group (DR-C, n = 8). In both groups, blood pressure was similar and significantly higher than in DR-C. Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSHF-V was significantly ameliorated in DSHF-IM using transthoracic echocardiography. The preproET-1, ETAR, and ACE mRNA levels in the left ventricle were significantly increased in DSHF-V compared with DR-C, and significantly suppressed in DSHF-IM compared with DSHF-V. DSHF-V demonstrated a significant increase in the wall-to-lumen ratio and perivascular fibrosis in coronary arterioles, and myocardial fibrosis, with all these parameters being significantly improved by imidapril. In conclusion, myocardial remodeling and heart failure in DS rats fed a high salt diet were significantly ameliorated by a subdepressor dose of imidapril, which may be attributable to a decrease in ET-1 mRNA expression and angiotensin II in the left ventricle.     

Effect of long-term ACE inhibition on myocardial tissue in hypertensive stroke-prone rats.

The aim of the study was to investigate the influence of long-term ACE inhibition with ramipril on myocardial hypertrophy and its molecular background in spontaneously hypertensive stroke-prone rats (SHR-SP). Therefore, 1-month-old pre-hypertensive SHR-SP were randomized into three groups and exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive dose, RHI), 10 micrograms/kg/day ramipril (non-anti-hypertensive dose, RLO) or placebo. After 15 months cardiac tissue was collected from ten rats each for immunohistochemistry and Northern blot analysis of structural proteins, proteins of the extracellular matrix and several growth factors. Results showed that RHI, but not RLO, treatment prevented development of myocyte hypertrophy (ANP). Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no evidence of degeneration and loss of structural proteins (alpha -actinin), inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins (collagen, fibronectin, vimentin). Only in RHI-treated animals, mRNA levels for TGF- beta(1)as well as of collagen alpha(1)(I) and fibronectin were downregulated compared to placebo-treated animals. In contrast, VEGF mRNA levels increased significantly in both groups of ramipril-treated animals v. placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses of ramipril which is associated with prevention of hypertension and hypertrophy is accompanied by prevention of the development of necrosis and fibrosis. The role of VEGF, however, seems to be independent of this effect.     

心肌梗死后心肌T型钙通道基因表达及在心肌重塑中的作用

目的 :探讨心肌梗死后心肌重塑过程中T型钙通道基因表达的变化及其在心肌重塑中的作用。方法 :Wistar大鼠 18只 ,随机分为心肌梗死后 3h、2 1d组及假手术组 3组 ,每组各 6只 ,建立心肌梗死后心肌重塑模型。假手术组不结扎冠状动脉。采用RT PCR方法检测T型钙通道基因表达的变化 ;采用免疫组织化学方法染色和计算机图像分析方法检测Ⅰ型、Ⅲ型胶原和纤维连接蛋白 (FN)表达的变化 ;采用原子吸收光谱法测定心肌总Ca2 + 浓度。结果 :心肌梗死后 2 1d心肌重塑过程T型钙通道基因在邻近梗死区非梗死心肌表达 ,而远离梗死区心肌不表达 ;假手术组不出现表达。心肌Ⅰ型、Ⅲ型胶原 ,FN在梗死组心肌显著表达 ,与假手术组比较差异有显著性意义 (P <0 .0 5或 <0 .0 1)。心肌总Ca2 + 测定显示 ,梗死组比假手术组明显增加 (P <0 .0 5 )。结论 :T型钙通道与心肌梗死后心肌重塑密切相关。钙通道基因表达的意义可能在于增加心肌细胞膜钙通道密度。Ca2 + 经过钙通道进入细胞触发心肌重塑过程。提示 ,临床上开发和利用T型钙通道阻滞剂对防治心肌梗死后心肌重塑、心力衰竭和心律失常具有重要价值     

Adventitial remodeling after angioplasty is associated with expression of tenascin mRNA by adventitial myofibroblasts

OBJECTIVES: The purpose of this study was to determine the temporospatial expression of tenascin-C (TnC) in balloon-injured rat and porcine arteries. BACKGROUND: Recent studies suggest that cell migration, in addition to cell proliferation, is a critical component of neointima formation after vascular injury. We have previously shown that adventitial myofibroblasts synthesize growth factors that contribute to the formation of neointima after arterial injury. We have also shown that the extracellular matrix protein, TnC, regulates cell migration. Consequently, we investigated the temporospatial expression of TnC by myofibroblasts after vascular injury. METHODS: In situ hybridization and immunohistochemistry were used to investigate the temporospatial expression of TnC in injured arteries. Northern and Western blots were used to determine the in vitro expression of TnC. RESULTS: In situ hybridization revealed that the major site of TnC expression early after vascular injury was the adventitial myofibroblasts. Immunohistochemical staining demonstrated that TnC expression began in adventitial myofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascular wall toward the luminal surface. By one week, TnC expression reached the developing neointima. In vitro, myofibroblasts did not express TnC mRNA under basal conditions. In contrast, angiotensin II and PDGF-BB, factors that have been implicated in remodeling of balloon-injured arteries, markedly upregulated TnC mRNA. CONCLUSIONS: Tenascin-C is expressed in response to balloon injury. Tenascin-C expression begins with adventitial myofibroblasts. Over a period of 7 to 14 days, expression moves progressively across the vessel wall to the neointima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling.     

Training-induced pressure fall in spontaneously hypertensive rats is associated with reduced angiotensinogen mRNA expression within the nucleus tractus solitarii

Knowing that exercise training reduces arterial pressure in hypertensive individuals and that pressure fall is accompanied by blockade of brain renin-angiotensin system, we sought to investigate whether training (T) affects central renin-angiotensin system. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto controls (WKY) were submitted to training or kept sedentary (S) for 3 months. After functional recordings, brain was removed and processed for autoradiography (brain stem sequential slices hybridized with (35)S-oligodeoxynucleotide probes for angiotensinogen [Aogen] and angiotensin II type 1 [AT(1A)] receptors). Resting arterial pressure and heart rate were higher in SHR(S) (177+/-2 mm Hg, 357+/-12 bpm versus 121+/-1 mm Hg, 320+/-9 bpm in WKY(S); P<0.05). Training was equally effective to enhance treadmill performance and to cause resting bradycardia (-10%) in both groups. Training-induced blood pressure fall (-6.3%) was observed only in SHR(T). In SHR(S) (versus WKY(S)) AT(1A) and Aogen mRNA expression were significantly increased within the NTS and area postrema (average of +67% and +41% for AT(1A) and Aogen, respectively; P<0.05) but unchanged in the gracilis nucleus. Training did not change AT(1A) expression but reduced NTS and area postrema Aogen mRNA densities specifically in SHR(T) (P<0.05 versus SHR(S), with values within the range of WKY groups). In SHRs, NTS Aogen mRNA expression was correlated with resting pressure (y=5.95x +41; r=0.55; P<0.05), with no significant correlation in the WKY group. Concurrent training-induced reductions of both Aogen mRNA expression in brain stem cardiovascular-controlling areas and mean arterial pressure only in SHRs suggest that training is as efficient as the renin-angiotensin blockers to reduce brain renin-angiotensin system overactivity and to decrease arterial pressure.     

血管紧张素转化酶基因的插入/缺失多态性与其血清水平及心肌梗塞的关系

旨在探讨中国人中血管紧张素转化酶（ＡＣＥ）基因的插入／缺失（ｉｎｓｅｒｔｉｏｎ／ｄｅｌｅｔｉｏｎ，Ｉ／Ｄ）多态性与血清中ＡＣＥ水平及心肌梗塞的关系。心肌梗塞患者１０３例；正常对照９６例。位于ＡＣＥ基因第１６内含子的Ｉ／Ｄ多态性经ＰＣＲ扩增可分为三种基因型：纯合缺失型（ＤＤ），纯合插入型（Ｉ），杂合子型（ＩＤ）。血清ＡＣＥ水平在ＤＤ、ＤＩ、Ｉ型分别为２８．３±９．９Ｕ／ｍｌ、２４．５±８．４Ｕ／ｍｌ、１９．２±４．８Ｕ／ｍｌ，即ＤＤ＞ＤＩ＞ⅠⅠ。结果显示，心肌梗塞患者的Ｄ等位基因的频率（０．６１）高于正常对照组（０．４８），Ｐ＜０．０１。认为：ＡＣＥ基因的缺失多态性与中国人血清ＡＣＥ水平及心肌梗塞相关。     

全反式维甲酸对高血压大鼠体内ACE2表达与一氧化氮信号的影响

目的:探讨全反式维甲酸(atRA)对高血压大鼠体内血管紧张素转换酶2(ACE 2)基因表达及一氧化氮(NO)信号的影响。方法:采用自发性高血压大鼠(SHR)及其同源对照W KY大鼠,经腹腔注射atRA,为期1月。分别用实时荧光定量PCR,N orthern印迹及免疫印迹技术测定atRA治疗后SHR体内ACE 2、血管紧张素Ⅱ1型受体(AT1)的表达情况,以硝酸还原酶法检测血清NO水平。结果:与W KY对照组相比,SHR心脏ACE 2的mRNA和蛋白表达下调[mRNA拷贝数比值:(0.06±0.02)vs.1;蛋白吸光度比值:(0.73±0.05)vs.1,P均<0.01],atRA(低、高剂量atRA组)治疗后SHR心脏ACE 2表达上调[mRNA:(0.23±0.08),(0.53±0.18)vs.(0.06±0.02);蛋白水平上升:(0.9±0.07),(0.92±0.08)vs.(0.73±0.05),P均<0.05],同时出现AT1表达降低、血清NO水平增高以及血压下降(P均<0.05)。结论:长期atRA治疗促进SHR大鼠心脏ACE 2的表达增加,导致体内NO增加,血压下降,提示转录调节剂atRA很可能对人类高血压病防治具有一定的价值。     

缬沙坦对心肌病大鼠肾脏及心肌中ACE2 mRNA、ACE mRNA表达的影响

目的:探讨阿霉素诱导的心肌病大鼠肾脏及心肌组织中血管紧张素转换酶2(ACE2)mRNA、血管紧张素转换酶(ACE)mRNA的表达及缬沙坦对其的影响.方法:30只Wistar大鼠随机分为3组:正常对照组即生理盐水组(n=10);生理盐水 阿霉素组(n=10);阿霉素 缬沙坦组(n=10).RT-PCR法检测肾、心肌组织中ACE2 mRNA、ACE mRNA的表达,光镜及透射电镜观察心肌病理变化. 结果:阿霉素组大鼠较正常对照组大鼠肾脏及心肌组织中ACE2 mRNA(3.35±0.39对2.21±0.18,P=0.000;2.50±0.29对1.25±0.13,P=0.000)、ACE mRNA(2.31±0.38对1.19±0.12,P=0.000;1.77±0.09对0.84±0.11,P=0.000)的表达均明显增高,缬沙坦治疗组大鼠肾脏及心肌组织中ACE2 mRNA(2.65±0.34对3.35±0.39,P=0.001;1.72±0.32对2.50±0.29,P=0.000)、ACE mRNA(1.68±0.1 5对2.31±0.38,P=0.004;1.21±0.10对1.77±0.09,P=0.000)的表达较阿霉素组明显降低. 结论:阿霉素诱导的心肌病大鼠肾脏及心肌组织中ACE2mRNA、ACE mRNA表达水平均显著高于正常大鼠;缬沙坦对于阿霉素诱导的心肌病大鼠肾脏及心肌具有保护作用.     

当归挥发油对自发性高血压大鼠ACE2基因表达的影响

目的探讨当归挥发油对自发性高血压大鼠(SHR)心肌血肌紧张素转换酶(ACE)2基因表达的影响及作用机制。方法将40只8周龄雄性SHR随机分为模型组,当归挥发油组(低、高)和卡托普利组,并以同周龄的Wistar大鼠作为正常对照组。分别灌胃4 w后,取大鼠心肌组织,HE染色观察心肌组织形态学的变化实时荧光定量PCR法检测ACE2 mRNA表达量,Western印迹检测ACE2蛋白的表达水平。结果当归可降低SHR血压;HE染色显示,与模型组相比较,当归挥发油各组病变分别有不同程度的减轻;与模型组相比,当归高、低剂量组ACE2 mRNA及蛋白表达水平均明显升高(P<0.01)。结论当归挥发油对SHR血压有调节作用,可能通过ACE2基因发挥降压作用。     

Celiprolol stimulates endothelial nitric oxide synthase expression and improves myocardial remodeling in deoxycorticosterone acetate-salt hypertensive rats

OBJECTIVE: Endothelium-dependent vasodilation is attenuated in humans and experimental hypertension models, and this phenomenon may be largely due to decreased release or activity of nitric oxide (NO). However, very few studies have evaluated whether beta-adrenoceptor antagonists increase endothelial NO synthase (eNOS) expression in the left ventricle. We examined the effects of long-term treatment with celiprolol, a specific beta1-antagonist with a weak beta2-agonist action, on eNOS expression in the left ventricle and evaluated its relationship to myocardial remodeling in the left ventricle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: DOCA-salt rats (n = 18) were induced with weekly injections of DOCA (30 mg/kg) and 1% saline in their drinking water after right nephrectomy. Celiprolol (DOCA-CEL, n = 9, 10 mg/kg per day, subdepressor dose) or a vehicle (DOCA-V, n = 9) were given after induction of DOCA-salt hypertension for 5 weeks, and age-matched sham-operated rats (ShC, n = 9) served as a control group. RESULTS: Blood pressure levels in DOCA-V and DOCA-CEL were similar and significantly higher than that in ShC. The eNOS mRNA and protein levels, and NOS activity in the left ventricle significantly decreased in DOCA-V compared with ShC, and significantly increased in DOCA-CEL compared with DOCA-V. DOCA-V showed a significant increase in the wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and type I collagen mRNA, with all these parameters being significantly improved by celiprolol. CONCLUSIONS: Myocardial remodeling of DOCA-salt hypertensive rats was significantly ameliorated by subdepressor doses of celiprolol, which may be due to increased eNOS expression in the left ventricle.     

缬沙坦对心肌病大鼠肾脏及心肌中ACE2 mRNA、ACE mRNA表达的影响

目的：探讨阿霉素诱导的心肌病大鼠肾脏及心肌组织中血管紧张素转换酶2(ACE2)mRNA、血管紧张素转换酶(ACE)mRNA的表达及缬沙坦对其的影响。方法：30只Wistar大鼠随机分为3组：正常对照组即生理盐水组(n=10)；生理盐水 阿霉素组(n=10)；阿霉素 缬沙坦组(n=10)。RT-PCR法检测肾、心肌组织中ACE2 mRNA、ACE mRNA的表达,光镜及透射电镜观察心肌病理变化。结果：阿霉素组大鼠较正常对照组大鼠肾脏及心肌组织中ACE2 mRNA(3．35±0．39对2．21±0．18,P=0．000；2．50±0．29对1．25±0．13,P=0．000)、ACE mRNA (2．31±0．38对1．19±0．12,P=0．000；1．77±0．09对0．84±0．11,P=0．000)的表达均明显增高,缬沙坦治疗组大鼠肾脏及心肌组织中ACE2 mRNA(2．65±0．34对3．35±0．39,P=0．001；1．72±0．32对2．50±0．29,P=0．000)、ACE mRNA (1．68±0．15对2．31±0．38,P=0．004；1．21±0．10对1．77±0．09,P=0．000)的表达较阿霉素组明显降低。结论：阿霉素诱导的心肌病大鼠肾脏及心肌组织中ACE2 mRNA、ACE mRNA表达水平均显著高于正常大鼠；缬沙坦对于阿霉素诱导的心肌病大鼠肾脏及心肌具有保护作用。     

己酮可可碱对内毒素血症大鼠心肌组织TNF-α基因表达的影响

目的 :观察己酮可可碱 （ PTX）对内毒素血症 （ ETM）大鼠心肌组织肿瘤坏死因子 -α（ TNF-α）基因表达的影响 ,探讨 PTX对 ETM大鼠心肌组织可能的保护机制。方法 :以 ETM大鼠为模型 ,动物随机分为 ETM模型组 （ 12只 ）和 PTX干预组 （ 12只 ）。采用逆转录聚合酶链反应 （ RT-PCR）和放射免疫分析法分别检测不同时间点心肌组织TNF-α m RNA表达水平及血循环 TNF-α含量。结果 :PTX干预后 ,心肌组织 TNF-α基因表达及血循环 TNF-α含量均受到不同程度抑制 （ P<0 .0 5 ,P<0 .0 1）。结论 :PTX能有效抑制 ETM大鼠心肌 TNF-α基因表达 ,为 PTX保护 ETM心肌组织提供了实验依据     

Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

ObjectiveTo investigate the effects of Xinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.MethodsSixty Wistar rats were randomly divided into four groups. The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method. Rats in A and B groups were intragastrically administered with physiological saline, while C and D groups were administered with Xinjikang and metoprolol, respectively. The changes in blood pressure, E/A ratio, myocardial pathological morphology, myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment.ResultsThere were statistically significant differences in E/A ratio between C group after treatment and model group (P<0.05), while no difference was observed between A and D groups (P>0.05); after treatment the myocardial lipoperoxides and superoxide dismustase contents in C and D groups were improved significantly compared with model group (P<0.05).ConclusionsXinjikang can improve myocardial injury, restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.     

Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats

Background

Farnesyltransferase (FT), an essential enzyme at the downstream of mevalonate pathway, was reported to be upregulated in hypertrophic cardiomyocytes of spontaneously hypertensive rats (SHRs) compared with myocardium of Wistar-Kyoto rats (WKYs). This upregulation was accompanied with cardiac remodeling. This study was designed to determine whether FT inhibition can alter cardiac remodeling in SHRs.

Methods

Twelve-week-old SHRs were randomized to receive infusion of either NS or FTI-276 (307 μg/kg/d i.v. each n = 10). WKY rats served as normal controls (n = 6). Echocardiography was performed before and after intervention. SHR hearts were perfused ex vivo for the evaluation of cardiac performance, collagen deposition and biochemical changes (activation of Ras, extracellular-signal regulated kinases/ERK1/2, procollagen type ?/Ш, TGF-β1, connective tissue growth factor/CTGF, and bone morphogenetic protein-7/BMP-7 expression).

Results

FTI-276 intervention decreased interventricular septum wall thickness at end- diastole (IVSd) and relative wall thickness (RWT) of SHRs (P< 0.05). Three week intervention with FTI-276 attenuated hydroxyproline content (P < 0.05), collagen deposition (P < 0.01), Ras activation, ERK1/2 phosphorylation (P < 0.01) and mRNA expression of procollagen type I, TGF-β1 and CTGF and elevated mRNA expression of BMP-7 (P < 0.05) in left ventricle of SHRs.

Conclusion

The present study indicated that FT inhibition could attenuate myocardial fibrosis and partly improve cardiac remodeling in SHRs. The beneficial effects might be mediated through suppression of the activation of Ras and ERK1/2 phosphorylation pathway. The enhanced mRNA expression of BMP-7 with inhibition of TGF-β1 and CTGF mRNA expression might be an important mechanism.     

Modification of myosin gene expression by imidapril in failing heart due to myocardial infarction

The beneficial effects of imidapril, an angiotensin converting enzyme (ACE) inhibitor were investigated on changes in myofibrillar ATPase as well as myosin heavy chain (MHC) content and gene expression due to myocardial infarction (MI). Three weeks after occluding the left coronary artery, rats were treated with or without imidapril (1 mg/kg/day), for 4 weeks. The infarcted hearts exhibited depressed rates of left ventricular (LV) pressure development (57+/-2.4% reduction) and pressure decay (55.5+/-1.6% reduction). LV myofibrillar Ca(2+) ATPase activity, unlike that in the right ventricle (RV), was decreased in the infarcted animals compared with controls (6.8+/-0.4 vs 10.3+/-0.6 micromol Pi/mg/hr). MHC alpha-isoform contents were decreased by 47 and 41% whereas those of MHC beta-isoform were increased by 823 and 1200% in the LV and RV due to MI, respectively. MHC alpha-isoform mRNA levels were decreased by 55 and 35% whereas those for MHC beta-isoform were increased by 50 and 30% in the infarcted LV and RV, respectively. Imidapril treatment partially prevented the changes due to MI in LV function (rate of pressure development, 24+/-2.3% reduction and rate of pressure decay, 14+/-1.8% reduction), myofibrillar Ca(2+) ATPase activity (8.2+/-0.7 micromol Pi/mg/hr), MHC protein content (alpha-MHC, 24% reduction and beta-MHC, 525% increase) and MHC gene expression (alpha-MHC, 18% reduction and beta-MHC, 15% increase). The results suggest that the beneficial effects of ACE inhibition on the failing heart are associated with improvements in myofibrillar ATPase activities as well as prevention of changes in MHC isozyme protein contents and their gene expression.     

Type 2 diabetes is associated with left ventricular concentric remodeling in hypertensive patients

BACKGROUND: Left ventricular (LV) geometric remodeling is associated with cardiovascular prognosis in hypertensive patients. It is uncertain how LV remodeling is modulated by diabetes in hypertensive patients. In this study, we investigated the impact of diabetes and ambulatory blood pressure (BP) on LV geometric remodeling in hyptensives with/without diabetes. METHODS: Ambulatory BP monitoring and echocardiography were performed to compare 24-h BP levels and LV measurements in 400 uncomplicated hypertensives (mean age, 67 years, 152 men and 248 women) between diabetic (n = 161) and nondiabetic (n = 239) patients. RESULTS: The age (67 v 68 years), percentage of men (43% v 34%), body mass index (24.5 v 24.0 kg/m(2)), 24-h systolic BP (144/80 v 144/82 mm Hg), LV mass index (128 v 130 g/m(2)) were similar between the groups. Diabetic patients had higher relative wall thickness (0.50 v 0.44, P < .001) and higher prevalence of concentric LV hypertrophy (39.4% v 26.8%, P < .001) than nondiabetic patients. The presence of diabetes (odds ratio [OR] = 2.76; 95% confidence interval [CI] = 1.73-4.41, P < .001) and 24-h systolic BP (OR for 10 mm Hg increase = 1.17; 95% CI = 1.01-1.37, P < .05) were independently associated with the higher relative wall thickness (>/=0.45). On the other hand, 24-h systolic BP was independently associated with LV hypertrophy (OR for 10 mm Hg increase = 1.32; 95% CI = 1.14-1.52, P < .05). CONCLUSIONS: Among hypertensive patients, type 2 diabetes was associated with concentric LV geometry independent of ambulatory BP.     

The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS- than in saline-treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.