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At least 19 recordsLinked to original sources
PubMed1998

Inotropic response of stunned hypertrophied myocardium: responsiveness of hypertrophied and normal postischemic isolated rat hearts to calcium and dopamine stimulation.

OBJECTIVE: Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca(2+)-responsiveness are reported. Information sensitivity to reversible ischemia and on postischemic Ca(2+)-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study. METHODS AND RESULTS: Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+ 50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78 +/- 1% and 77 +/- 3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95 +/- 2% in hypertrophied and 93 +/- 3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124 +/- 4% in hypertrophied and 120 +/- 5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138 +/- 3% and 157 +/- 5%, respectively ( p < 0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose-response curve for Ca(2+)-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values. CONCLUSION: The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the beta-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.

Analysis of Variance↗
PubMed1998

Clinicopathologic heterogeneity in hypertrophic cardiomyopathy with regard to age, asymmetric septal hypertrophy, and concentric hypertrophy beyond the pediatric age group.

BACKGROUND: To our knowledge, no histopathologic study of the differences between hypertrophic cardiomyopathy in different age groups or that contrasts the pathologic findings in the asymmetric septal hypertrophy and concentric hypertrophy forms of hypertrophic cardiomyopathy has been published. METHODS: The clinicopathologic findings of younger (< or =60 years) (n = 35) and older (>60 years) (n = 20) patients with hypertrophic cardiomyopathy were assessed. Each group was subdivided into groups of patients with asymmetric septal hypertrophy or concentric hypertrophy. RESULTS: Among the young patients, asymmetric septal hypertrophy was more prevalent than concentric hypertrophy, whereas among the elderly patients, concentric hypertrophy was more common. Sudden death was prevalent only among the young. Most young patients had a mirror-image endocardial fibrous septal plaque, whereas most elderly patients with concentric hypertrophy did not. Ventricular septal myocyte disarray and intramural coronary artery thickening were far more marked among the young with asymmetric septal hypertrophy than the young with concentric hypertrophy and the elderly. CONCLUSIONS: Key differences exist between younger and older patients with hypertrophic cardiomyopathy. Much higher degrees of ventricular disarray and intramural coronary artery disease were noted in younger patients with asymmetric septal hypertrophy compared to the elderly patients and the younger patients with concentric hypertrophy.

Adult↗
PubMed1998

Energy generation in hypertrophied postischemic myocardium. Feasibility of prolonged inotropic stimulation with dopamine in hypertrophied reperfused left ventricles.

BACKGROUND: Non-hypertrophied reversibly injured postischemic myocardium can be stimulated for a prolonged period without detrimental effects. Since no data on hypertrophied myocardium are available, our aim was to examine the effects of a prolonged postischemic positive inotropic stimulation on moderately hypertrophied left ventricles. METHODS: Using a Langendorff-type isovolumically contracting isolated heart model, moderately hypertrophied (+50% of ventricular mass) hearts from spontaneously hypertensive rats (SHR) were investigated and compared to data from non-hypertrophied hearts of normotensive rats. A 30 minutes noflow ischemia was performed, and in the postischemic period dopamine was continuously administered for 20 minutes in order to stimulate the postischemic hearts to the control level of function. Data were compared to postischemic hearts without stimulation and to non-ischemic controls. After 50 minutes of reperfusion and cessation of the catecholamine steady state function, maximum contractile response, and high energy phosphates were determined. RESULTS: 30 minutes ischemia followed by 50 minutes reperfusion caused a significant reduction in developed LVP to 77.8 +/- 4.2% in SHR. Dp/dtmax was reduced to 67.0 +/- 2.3%. After cessation of dopamine stimulation developed LVP was 64.3 +/- 3.5% and dp/dtmax 69.3 +/- 3.7% in SHR. The double product was identically reduced in all postischemic groups. The contractile reserve was comparable in stimulated and non-stimulated postischemic SHR hearts. In hypertrophied myocardium, ATP was reduced to 1.1 +/- 0.1 mumol/gww (non-ischemic controls 2.5 +/- 0.3 mumol/gww) in unstimulated and to 1.0 +/- 0.1 mumol/gww in stimulated postischemic hearts. Comparably the ischemia-induced reduction in ATP in non-hypertrophied myocardium was 1.3 mumol/gww. Similar results were obtained for ADP and AMP. Creatine phosphate levels were normal in stimulated and non-stimulated postischemic myocardium of hypertrophied and non-hypertrophied hearts. CONCLUSION: These results indicate that prolonged stimulation of stunned hypertrophied myocardium is feasible without detrimental effects on post-stimulation contractile function. The energy generating apparatus is capable to deliver sufficient energy during stimulation of stunned hypertrophied hearts.

Adenosine Diphosphate↗
PubMed1996

Electrocardiographic identification of left ventricular hypertrophy: test performance in relation to definition of hypertrophy and presence of obesity.

OBJECTIVES: This study sought to assess a test performance of the electrocardiogram (ECG) in relation to 1) varying definitions of left ventricular hypertrophy based on different methods of adjusting left ventricular mass for body size, and 2) the presence or absence of obesity. BACKGROUND: Although left ventricular mass is most commonly indexed for body surface area or height when defining left ventricular hypertrophy, recent work suggests that normalization for height to the power of 2.7 (height2.7) may decrease variability among normal subjects and correctly identify the impact of obesity on hypertrophy. METHODS: The product of Cornell voltage and QRS duration (Cornell product) and Framingham-adjusted Cornell voltage were determined from 12-lead ECGs in 212 patients. Left ventricular hypertrophy was defined on the basis of left ventricular mass indexed to body surface area, height and height2.7. RESULTS: Using partitions with matched specificity of 95%, the sensitivity of ECG criteria varied with the definition of hypertrophy, ranging from 39% to 52% for the Cornell product and from 24% to 33% for adjusted Cornell voltage. When left ventricular mass was indexed to body surface area or to height2.7, the 52% and 39% sensitivities of the Cornell product were significantly greater than the 24% (p < 0.001) and 29% (p < 0.05) sensitivities of adjusted Cornell voltage, with a similar trend when left ventricular mass was indexed to height (43% vs. 33%, p = 0.10). Comparison of receiver operating characteristic curves confirmed the superior overall performance of the Cornell product relative to adjusted Cornell voltage for hypertrophy defined by body surface area and height2.7 and demonstrated greater reproducibility of overall performance, as measured by the coefficient of variability, for the Cornell product (1.7%) than for adjusted Cornell voltage (5.8%). Sensitivity of adjusted Cornell voltage was significantly greater in obese than in nonobese subjects (50% to 59% vs. 18% to 24%, p < 0.01), but the Cornell product had only minimally higher sensitivity in nonobese than in obese subjects (40% to 54% vs. 32% to 44%, p = NS). CONCLUSIONS: The ability of ECG criteria to detect left ventricular hypertrophy differs depending on the method of indexing left ventricular mass for body size and with the presence or absence of obesity. Further, the Cornell product provides the best combination of overall accuracy and low variability of performance between definitions of hypertrophy. These findings have important implications for the clinical and epidemiologic use of 12-lead ECG criteria for the detection of left ventricular hypertrophy.

Adult↗
PubMed1998

Proliferating cell nuclear antigen in hypertrophied spinal ligaments. Immunohistochemical localization of proliferating cell nuclear antigen in hypertrophied posterior longitudinal ligament of the cervical spine.

STUDY DESIGN: An experimental immunohistochemical investigation using an antibody for proliferating cell nuclear antigen. Surgically-extirpated specimens of posterior longitudinal ligament tissues from patients with hypertrophy of the posterior longitudinal ligament and other disorders of the cervical spine were analyzed. OBJECTIVE: To analyze the developmental mechanism of hypertrophy of the posterior longitudinal ligament, the authors evaluated the growth activity of cells in the posterior longitudinal ligament tissues by examining the immunolocalization of the proliferating cell nuclear antigen. SUMMARY OF BACKGROUND DATA: Although a number of cases of hypertrophy of the posterior longitudinal ligament have been reported, the pathophysiology of ligament hypertrophy is still unclear. It is well established that the proliferating cell nuclear antigen is a cell proliferation marker, and immunohistochemical analysis using an anti-proliferating cell nuclear antigen antibody is of value in assessing the cell growth activity of several tissues. METHODS: During anterior decompression surgery in the cervical spine, the authors extirpated posterior longitudinal ligament tissues in one piece from patients with hypertrophy of the posterior longitudinal ligament, ossification of the posterior longitudinal ligament, cervical disc herniation, and cervical spondylotic myelopathy. Midsagittal sections of the specimens were stained with an antibody against the proliferating cell nuclear antigen. RESULTS: In cases of hypertrophy of the posterior longitudinal ligament, immunostaining with the proliferating cell nuclear antigen was detected in cells in the posterior longitudinal ligament, not only at the vertebral endplate level, but also at the midvertebral level. A similar distribution of proliferating cell nuclear antigen-positive cells was observed in cases of ossification of the posterior longitudinal ligament. In cases of cervical disc herniation, however, proliferating cell nuclear antigen-positive cells in posterior longitudinal ligament tissues were restricted to the vertebral endplate level. No immunostaining with the proliferating cell nuclear antigen was seen in posterior longitudinal ligament tissues in cases of cervical spondylotic myelopathy. CONCLUSIONS: Cell growth activity was accelerated in posterior longitudinal ligament tissues in cases of hypertrophy of the posterior longitudinal ligament; such an unusual phenotype of posterior longitudinal ligament cells was also expressed in cases of ossification of cervical disc herniation and cervical spondylotic myelopathy. Therefore, up-regulation of the growth of posterior longitudinal ligament cells may contribute to the development of hypertrophy of the posterior longitudinal ligament, and some common regulatory mechanism(s) on the proliferation of posterior longitudinal ligament cells seem to underlie the development of hypertrophy of the posterior longitudinal ligament and ossification of the posterior longitudinal ligament.

Adult↗
PubMed2003

Increased insulin-like growth factor-I gene expression precedes left ventricular cardiomyocyte hypertrophy in a rapidly-hypertrophying rat model system.

Chronic pressure overload leads to an increase in the size, i.e. hypertrophy, of cardiomyocytes in the heart. However, the molecular mechanisms underlying this hypertrophy are not understood. Insulin-like growth factor-I (IGF-I) synthesized locally in the heart is known to be associated with the hypertrophic process. So far, however, cardiac IGF-I gene expression in the widely used rat model system has only been shown to be increased when the hypertrophy induced by pressure-overload was already established. Therefore, the question of whether IGF-I serves as an initiating or early-enhancing factor for the cardiac hypertrophy remains unanswered. Here, cardiac hypertension and hypertrophy were rapidly induced in the rat by complete constriction of the abdominal aorta between the origins of the renal arteries. Carotid arterial systolic blood pressure remained unchanged in sham rats but increased rapidly in the pressure-overloaded constricted rats with a sustained hypertension established by 3 days. Hypertrophy of left ventricular (LV) cardiomyocytes in constricted rats also occurred by 3 days. However, this hypertrophy was preceded by increases in LV IGF-I mRNA and protein which occurred within 1 day. These results support the hypothesis that cardiac-synthesized IGF-I is an initiating or early-enhancing factor for hypertrophy of LV cardiomyocytes.

Animals↗
PubMed2001

Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy.

OBJECTIVES: This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure. BACKGROUND: Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation. METHODS: Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study. RESULTS: From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats. CONCLUSIONS: Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.

Animals↗
PubMed2001

[Can pathological left ventricular hypertrophy in arterial hypertension be distinguished from physiological hypertrophy caused by sports?].

BACKGROUND AND OBJECTIVE: Patients with hypertensive heart disease and left ventricular hypertrophy demonstrate impaired left ventricular diastolic filling. Aim of this study was to find out if physiological left ventricular hypertrophy induced by endurance training causes abnormal left ventricular systolic and diastolic filling. METHODS: We examined 42 athletes with left ventricular hypertrophy due to endurance training (aged 25 +/- 7 years), 31 patients with left ventricular hypertrophy due to hypertensive heart disease (aged 28 +/- 6 years) and 20 untrained, healthy subjects (controls, aged 26 +/- 8 years) by conventional echocardiography and calculated left ventricular muscle mass and fractional shortening. In addition the following Doppler-echocardiographic parameters were measured: maximal early and late velocity of diastolic filling, ratio of maximal early and late velocity of diastolic filling, acceleration and deceleration time and isovolumetric relaxation time. RESULTS: All three study groups showed normal fractional shortening. Conventional echocardiography revealed a higher left ventricular muscle mass in the two study groups as compared to the controls (controls: 119 +/- 12 g, athletes: 225 +/- 18 g*; hypertensive patients: 216 +/- 16 g*; * p < 0.01 versus controls). In the athletes with physiological left ventricular hypertrophy a normal left ventricular diastolic filling pattern was documented (VE: 0.64 +/- 0.1 m/s; VA: 0.51 +/- 0.2 m/s). In hypertensive heart disease a diastolic dysfunction in terms of a delayed relaxation pattern with a decrease of maximal early velocity of diastolic filling (VE: 0.45 +/- 0.09 m/s) and a compensatory increase of the maximal late velocity of diastolic filling (VA: 0.54 +/- 0.1 m/s) was demonstrated. CONCLUSION: In pathological left ventricular hypertrophy due to hypertensive heart disease a pathological diastolic filling pattern was documented. In athletes with physiological left ventricular hypertrophy a normal left ventricular diastolic filling pattern was revealed. Thus Doppler-echocardiographic parameters of left ventricular diastolic function can be of diagnostic importance for discriminating between pathological and physiological left ventricular hypertrophy.

Adolescent↗
PubMed2001

Overexpression of cdk Inhibitor p16INK4a by adenovirus vector inhibits cardiac hypertrophy in vitro and in vivo: a novel strategy for the gene therapy of cardiac hypertrophy.

Cardiac hypertrophy is one of the serious complications which increase mortality due to cardiovascular diseases. However, only a partial reduction of cardiac hypertrophy has been successful using current drug therapy. We demonstrate here reduction of cardiac hypertrophy in vitro and in vivo using an adenovirus vector encoding cyclin-dependent kinase (cdk) inhibitor p16INK4a. Adenovirus-mediated overexpression of cdk inhibitor p16INK4a completely inhibited cardiac myocyte hypertrophy induced by endothelin (ET)-1, as evaluated by [3H]leucine incorporation into the cells and mRNA levels of skeletal alpha -actin (SK-A) or atrial natriuretic peptide (ANP) as well as by morphometric analyses. We then evaluated whether p16INK4a can suppress left-ventricular (LV) hypertrophy induced by aortic banding (AOB) in rats. Catheter-mediated gene transfer of AxCAp16 was performed according to the method reported by Hajjar et al. LV overload was produced by coarctation of the ascending aorta immediately after inoculation of the heart with adenovirus. Two weeks after the procedure, the left ventricular weight/body weight ratio (LVW/BW) increased in the AOB+LacZ group in comparison to that in controls. However, LVW/BW was identical in the AOB+p16 group and controls. Histologic analysis revealed that p16INK4a inhibited hypertrophy of cardiac myocytes. These results suggest that G1 cell cycle regulators may restrict cardiac hypertrophy, and offer a novel strategy for the gene therapy of cardiac hypertrophy.

Actins↗
PubMed1999

Semiquantitative evaluation of alpha1A-adrenoceptor subtype mRNA in human hypertrophied and non-hypertrophied prostates: regional comparison.

The main purpose of this study was to compare semiquantitatively the amount of alpha1a-adrenoceptor subtype mRNA in urethral, central and peripheral areas in benign hypertrophied prostates and non-hypertrophied prostate by the competitive reverse transcriptase polymerase chain reaction (RT-PCR) method. Prostates from twenty cases of men with benign prostatic hypertrophy (BPH) and 5 cases of bladder tumor without BPH were obtained for this study. The mRNA was extracted from the urethral, central and peripheral areas of each prostate, and quantitative RT-PCR was performed using the ratio of PCR product of alpha1a-adrenoceptor mRNA/beta2-microglobulin mRNA. The ratio for the central area of the hypertrophied prostate was significantly greater than that for the same area of the non-hypertrophied prostate (p < 0.05). In contrast, the urethral area showed no significant difference between the two prostate conditions. The central area of the hypertrophied prostate showed the tendency to have an increased alpha1a-adrenoceptor mRNA level compared with the urethral area, though no statistical difference was recognized because of the high standard error. Regional differences in the alpha1a-adrenoceptor mRNA in the non-hypertrophied prostate were rarely observed. The present finding demonstrates that the increased alpha1a-adrenoceptor mRNA content found in the hypertrophied prostate (1) was due to that in the central area.

Aged↗
PubMed2001

Beta-adrenergic receptors and calcium cycling proteins in non-failing, hypertrophied and failing human hearts: transition from hypertrophy to failure.

Left ventricular hypertrophy may lead to heart failure. The transition between hypertrophy and heart failure is, however, incompletely understood. On the cellular level, human heart failure is characterized by alterations in Ca(2+)-cycling proteins and beta-adrenergic receptor density, but the hypertrophied human heart remains largely under studied. In this investigation, 21 donor hearts which could not be used for transplantation were studied. Ten of these hearts came from organ donors with documented left ventricular hypertrophy and normal cardiac function. Eleven of the hearts were non-failing, obtained from individuals with no evidence of cardiac disease. Nine failing hearts from transplant recipients were also studied. beta-adrenergic receptor density was determined by radioligand binding. mRNA for atrial natriuretic factor, calsequestrin, sarcoplasmic reticulum Ca(2+)-ATPase, and phospholamban was measured by Northern blot. Actin, calsequestrin, sarcoplasmic reticulum Ca(2+)-ATPase, and phospholamban proteins were quantified by Western blot. In both hypertrophied and failing ventricles, mRNA for atrial natriuretic factor was expressed, as compared to no expression in non-failing hearts. In failing hearts, beta -adrenergic receptor density and both mRNA and protein levels of the Ca(2+)-ATPase were significantly decreased v non-failing hearts. By comparison, hypertrophied hearts showed a reduction in mRNA expression for both the Ca(2+)-ATPase and phospholamban with no change in the corresponding protein levels, and no change in beta-receptors. These data suggest that the previously demonstrated reduction in beta-adrenergic receptors and Ca(2+)-cycling proteins in the failing human heart may be features of the decompensated state, but are not found in human hearts with left ventricular hypertrophy and preserved systolic function.

Aged↗
PubMed1992

Hypertrophy and reversal of hypertrophy in rat pelvic ganglion neurons.

An experimental procedure which chronically reduces the lumen of the urethra in adult female rats produced distension of the bladder and conspicuous thickening of its wall, resulting within 6-8 weeks in a ten-fold increase in muscle weight (muscle hypertrophy). During this process, the neurons in the pelvic ganglion that innervate the bladder undergo a large increase in size (neuronal hypertrophy). The average neuronal volume increased by 83%; small neurons became less numerous and large neurons became more numerous than in controls, but there was no increase in the maximum neuronal size. Six weeks after re-operation and removal of the urethral obstruction, the weight of the bladder was reduced (although not quite to the control levels), while the average neuronal size reversed to values very close to controls. In separate experiments, the pelvic ganglion of one side was removed. The nerve fibres in the hemidenervated bladder sprouted, grew and spread to innervate the whole bladder. The neurons in the surviving pelvic ganglion hypertrophied, the average cell volume increasing by 50% in seven weeks. The experiments showed that: (i) the pelvic neurons of adult rats are capable of very extensive growth when the tissue they innervate (bladder muscle) undergoes hypertrophy; (ii) the neuronal hypertrophy is reversible. This was taken to imply that there are factors within the bladder, including trophic substances, that regulate nerve cell volume not only by inducing growth but also by inducing the opposite effect, a cell size reduction; (iii) unilateral ganglionectomy, which did not induce muscle hypertrophy but doubled the amount of muscle innervated by the contralateral ganglion, was followed by marked neuronal hypertrophy.

Animals↗
PubMed1994

Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro.

BACKGROUND: Previous studies have demonstrated that angiotensin II (Ang II) acts as a growth-promoting factor directly on cardiac myocytes and that angiotensin-converting enzyme inhibitor induces regression of hypertrophied hearts both in experimental animals and in humans. These results suggest that the renin-angiotensin system (RAS) is involved in the formation of left ventricular hypertrophy (LVH). To elucidate the role of RAS in the progression of cardiac hypertrophy, we evaluated the effect of an Ang II receptor antagonist on LVH in spontaneously hypertensive rats (SHRs) and investigated the molecular mechanisms by which antagonizing Ang II receptors reduces cell hypertrophy of myocytes using the in vitro model of mechanical stretch. METHODS AND RESULTS: In the in vivo study, we treated SHRs with the nonpeptide Ang II receptor antagonist TCV-116 (0.1, 1, or 10 mg/kg per day) or hydralazine (10 mg/kg per day). Blood pressure was measured by the tail-cuff method, and wall thickness of left ventricle was serially monitored using M-mode echocardiography. Rats were killed at the age of 13, 17, 21, or 25 weeks, and left ventricular (LV) weight, transverse diameter of cardiomyocytes, relative amount of V3 myosin heavy chain (MHC), and degree of interstitial collagen accumulation were examined. Untreated SHRs progressively developed severe hypertension, but treatment with TCV-116 or hydralazine inhibited the increase in blood pressure. Treatment with TCV-116 reduced LV weight, LV wall thickness, transverse diameter of myocytes, relative amount of V3 MHC, and interstitial fibrosis, whereas treatment with hydralazine slightly prevented an increase in LV wall thickness but did not exert significant reduction in other parameters. In the in vitro study, neonatal rat cardiomyocytes were cultured on deformable silicone dishes and mechanically stretched with or without pretreatment of CV-11974 (an active metabolite of TCV-116), and [3H]phenylalanine incorporation, activity of mitogen-activated protein (MAP) kinase, and c-fos mRNA expression were analyzed. Pretreatment of cultured cardiomyocytes with 10(-7) mol/L CV-11974 inhibited an increase in [3H]phenylalanine incorporation, MAP kinase activity, and c-fos gene expression induced by stretch of cardiomyocytes. CONCLUSIONS: The Ang II receptor antagonist TCV-116 induced regression of cardiac hypertrophy and had cardioprotective effects on hypertrophied myocardium in vivo, and antagonizing Ang II receptors inhibited intracellular signaling of stretch-mediated cardiomyocyte hypertrophy in vitro. These results suggest a crucial role of the cardiac RAS in the development of LVH produced by pressure overload.

Angiotensin II↗
PubMed1996

Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload.

Changes in contractile and relaxation properties of heart muscle in the cardiac hypertrophy induced by pressure overload have been attributed to alterations in intracellular Ca2+ transport as well as the phenotypic and quantitative changes in contractile protein. However, contradictory data have been reported regarding Ca2+ uptake, release and storage by the sarcoplasmic reticulum (SR). The purpose of this study was to evaluate the changes in SR Ca(2+)-ATPase, ryanodine receptor, calsequestrin and alpha-actin gene expression, and the changes in Ca2+ uptake capacity in various degrees of hypertrophied hearts due to pressure overload. Cardiac hypertrophy was produced in rats by placing a constricting clip (0.80 mm) around the suprarenal abdominal aorta for 8 days. The mRNA levels and Ca2+ uptake capacity were then measured as a function of the severity of cardiac hypertrophy. Ca(2+)-ATPase and ryanodine receptor mRNA levels were increased in mildly hypertrophied hearts but were diminished in severely hypertrophied hearts, showing a bimodal response to pressure overload, Ca2+ uptake capacity showed similar changes along with a positive correlation with Ca(2+)-ATPase mRNA level (r = 0.67, P < 0.001). In contrast, the level of calsequestrin mRNA expression was unaltered and that of alpha-actin was markedly increased over a range of severity of cardiac hypertrophy. These findings suggest that the expression of sarcoplasmic reticulum genes for Ca2+ uptake and release is up- or downregulated dependent on the degree of pressure overload. The gene for the SR Ca2+ storage protein, calsequestrin, might be under different control from these genes in pressure overload. Our findings suggest that the decrease in ratio of mRNAs encoding Ca2+ uptake and release proteins to those encoding contractile proteins could significantly contribute to the slowed contractile and relaxation properties seen in pressure-overloaded hearts.

Actins↗