Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hypertrophy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed2003

Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy.

Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.

Animals↗
PubMed1991

Circadian blood pressure pattern in patients with treated hypertension and left ventricular hypertrophy.

Left ventricular hypertrophy in hypertensives is an important determinant of prognosis. In the present study 45 patients with treated essential hypertension were divided into two groups: 23 patients had normal left ventricular dimension and 22 patients had echocardiographic signs of left ventricular hypertrophy (LVH). All patients were adequately treated during daytime, but ambulatory blood pressure monitoring showed a distinct abnormal pattern in the LVH group characterized by a lack of blood pressure reduction during the night; 16 of 22 patients with LVH had no blood pressure decline during the night, whereas 17 of 23 patients without hypertrophy showed this reduction (P less than 0.01). In conclusion, patients with hypertension and LVH often reveal a lack of blood pressure decline during the night, which may be the reason for the development of left ventricular hypertrophy (and thus should be managed by a different circadian blood pressure therapy) or which may be the consequence of progressive structural changes in the resistance vessels, along with the development of left ventricular hypertrophy. It is suggested that patients with hypertension and left ventricular hypertrophy should have ambulatory twenty-four hour blood pressure monitoring.

Antihypertensive Agents↗
PubMed2001

Expressions of bradykinin B2-receptor, kallikrein and kininogen mRNAs in the heart are altered in pressure-overload cardiac hypertrophy in mice.

Angiotensin-converting enzyme inhibitors prevent cardiac hypertrophy in vivo, and a component of this ameliorative effect has been attributed to accumulation of kinins in cardiac tissues. However, little is known regarding the levels of kallikrein-kinin components in the heart during the development of cardiac hypertrophy. The objectives of the present study were to define the effects of pressure-overload cardiac hypertrophy on cardiac levels of kininogen, kallikrein and bradykinin B2 receptor mRNAs. The pressure-overload induced by aortic constriction produced cardiac hypertrophy in mice after 14 and 28d, assessed from the increased ratios of heart weight to body weight and elevation of brain natriuretic peptide mRNA in the heart. B2 receptor mRNA rapidly decreased in the heart within 7 d after the operation, subsequently returning to those of sham-operated animals. In contrast, levels of both low-molecular-weight kininogen and tissue kallikrein mRNAs were increased 7, 14 and 28 d after aortic constriction. These findings suggest that the mechanical load or stretch in cardiac tissue by pressue-overload rapidly produces the downregulation of B2 receptor expression during the initial stage which may allow the promotion of cardiac hypertrophy induced by a mediation of hypertophic factors such as angiotensin II, while upregulation of kininogen and kallikrein mRNAs during the chronic stage may lead to an enhancement of local kinin generation in the heart, from which further progression of cardiac hypertrophy during later stages may be regulated.

Animals↗
PubMed1989

Study of cardiac hypertrophy--humoral factors that stimulate protein metabolism of cultured rat heart cells.

Recent extensive studies suggested that some humoral factors may contribute to the development and/or reversal of cardiac hypertrophy in hypertension. The purpose of this study is to examine whether there exists humoral factor(s) for cardiac hypertrophy in experimental perinephritic hypertension in dogs. Hypertension was induced by the method of Page with some modifications. Humoral factors were studied using a microassay system that was independent of pressure overload, hemodynamic effects, and other factors. L(-)-isoproterenol (ISO) and angiotensin II (AngII) increased the uptake of 3H-uridine into 10-day-old cultured heart cells. The maximal response to ISO or AngII was obtained by 10(-5) M ISO or 10(-10) M AngII, and the percent increments in the uptake of 3H-uridine was 38.4 +/- 20.4%, and 45.1 +/- 22.5%, respectively. Moreover, ISO, DL-noradrenaline, and AngII stimulated protein synthesis of 7-day-old or 14-day-old cultured heart cells in this order (9.5 +/- 1.5, 7.3 +/- 1.2, 2.0 +/- 0.5 micrograms/6 x 10(5) by 7-day-old heart cells; 23.8 +/- 8.3, 19.0 +/- 9.4, 4.4 +/- 1.1 micrograms/6 x 10(5) by 14-day-old heart cells). Heart and kidney extracts were obtained from experimental perinephritic hypertensive dogs and sham-operated dogs. The heart extract obtained from hypertrophied left ventricle (LV) of the experimental hypertensive dogs, but not of the sham-operated dogs, increased the uptake of 3H-uridine into 10-day-old heart cells. The mean percent increment in uptake of 3H-uridine induced by the hypertrophied LV heart extract at a final concentration of 5 x 10(-3)% V/V (1-3 micrograms) in different experiments was about 15%. High performance liquid chromatography (HPLC) demonstrated that the LV heart extract obtained from the perinephritic hypertensive dogs contained at least 16 molecules. Among them, one with a molecular weight of approximately 11,200 daltons stimulated uptake of both 3H-uridine and 14C-leucine into cultured heart cells. These results demonstrated that heart extract obtained from hypertrophied LV of perinephritic hypertensive dogs contained at least one factor which may induce and/or modulate myocardial hypertrophy in this model for hypertension.

Angiotensin II↗
PubMed1996

Effects of the endothelin ETA-receptor antagonist FR139317 on development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

We investigated the role of endothelin-1 (ET-1) in the development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Two weeks after the start of DOCA-salt treatment, the rats were divided into two groups and were given FR139317 [(R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]- carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)] propionyl]amino-3-(2-pyridyl) propionic acid], a specific ETA-receptor antagonist, or its vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Vehicle-treated DOCA-salt rats developed marked hypertension after 4 weeks. FR139317 significantly suppressed the increase in systolic blood pressure with values averaging 163 +/- 8 mmHg (P < 0.05 vs DOCA-salt rats receiving vehicle, 195 +/- 9 mmHg). Morphological studies in the rats given the vehicle showed vascular medial hypertrophy, with a significant increase in the wall area and wall-to-lumen ratio. A marked decrease in vascular wall hypertrophy was observed in the FR139317-treated DOCA-salt rats. The cardiac hypertrophy in DOCA-salt hypertensive rats was also significantly reduced by FR139317. Therefore, these results suggest that ET-1 plays an important role in the development of DOCA-salt hypertension presumably by stimulating the ETA receptor. In addition, we found that an ETA-receptor antagonist effectively reduced cardiovascular hypertrophy in the rats, so the cardiovascular hypertrophy noted in DOCA-salt hypertensive rats may be related to ET-1.

Analysis of Variance↗
PubMed2003

Cardiac hypertrophy by hypertension and exercise training exhibits different gene expression of enzymes in energy metabolism.

Hypertension-induced pathological cardiac hypertrophy (hypertensive heart) and exercise training-induced physiological cardiac hypertrophy (athletic heart) have differences in cardiac properties. We hypothesized that gene expression of energy metabolic enzymes differs between these two types of cardiac hypertrophy. To investigate whether mRNA expression of key enzymes in the long-chain fatty acid (FA), glucose, and lactic acid metabolic pathways differs between these two types of cardiac hypertrophy, we used the hearts of spontaneously hypertensive rats (SHR; 19 weeks old) as a model of the hypertensive heart, swim-trained rats (Trained; 19 weeks old, swimming training for 15 weeks) as a model of the athletic heart, and sedentary Wistar-Kyoto rats (Control; 19 weeks old). SHR developed hypertensive cardiac hypertrophy, of which cardiac function was deteriorated, whereas Trained rats developed an athletic heart, of which cardiac function was enhanced. The mRNA expression of CD36, which involved in uptake of long-chain FA, in the heart was almost never detected in the SHR group. Furthermore, the mRNA expression of key enzymes in the long-chain FA metabolic pathway (acyl CoA synthase [ACoAS], carnitine palmitoyl transferase [CPT]-I, CPT-II, and isocitrate dehydrogenase [ISCD]) in the heart was significantly higher in the SHR group compared with the Control group. The mRNA expression of ACoAS, CPT-I, ISCD, and CD36 in the heart did not differ between Trained group and Control group, whereas that of CPT-II in the Trained group was significantly higher compared with the Control group. The mRNA expression of key enzymes (phosphofructokinase and lactate dehydrogenase) in glycolytic metabolic pathway in the heart was markedly higher in the SHR group compared with the Control group, whereas these mRNA expressions did not differ between Trained group and Control group. These findings suggest that the molecular phenotypes in the energy metabolic system differ in hypertension-induced pathological and exercise training-induced physiological cardiac hypertrophy, and these differences may participate in the differences in cardiac function.

Animals↗
PubMed1999

Antagonism of the renin-angiotensin system, hypertrophy and gene expression in cardiac myocytes.

In response to humoral and mechanical stimuli, the myocardium adapts to increased work load through hypertrophy of individual muscle cells. Myocardial hypertrophy is characterized by an increase in cell size in the absence of cell division and is accompanied by changes in gene expression. Angiotensin II (Ang II), the effector peptide of the renin-angiotensin system (RAS), regulates volume and electrolyte homeostasis and is involved in cardiac and vascular growth in rats. In this review, the role of RAS in myocyte protein synthesis (myocyte hypertrophy) and in induction of gene expression will be discussed in rat cardiomyocytes in culture. Traditional RAS can be considered as a system in which circulating Ang II is delivered to target tissues or cells. However, a local RAS has also been described in cardiac cells and evidence has been accumulated for autocrine and/or paracrine pathways by which biological actions of Ang II can be mediated. These actions of Ang II are primarily mediated through Ang II receptors subtype I (AT1-R). When evaluating the effects of Ang II in situ, both changes in circulating levels and local production have to be taken into account. Contrasting results have been found concerning the in vitro effect of Ang II on the protein synthesis in cardiac myocytes and can be at least partly be attributed to methodological problems such as assay of de novo protein synthesis and isolation and separation procedure of cardiac myocytes. The Ang II-induced hypertrophic effect also depends on the existence of nonmyocytes in a cardiocyte culture. In rat cardiocytes, AngII also causes induction of many immediately-early genes (c-fos, c-jun, jun-B, Egr-1 and c-myc) and induces also late markers of cardiac hypertrophy (skeletal alpha-actin and atrial natriuretic peptide expression) and growth factors (TGF-beta 1 gene expression). In vivo AngII via AT1-R, causes not only ventricular hypertrophy but also a shift to the fetal phenotype of the myocardium. Angiotensin-converting enzyme inhibitors and AngII receptor antagonists of the subtype I not only induce the regression but also prevent the development of cardiac hypertrophy in experimental rat models.

Animals↗
PubMed1985

Reversal of left ventricular hypertrophy by drug treatment of hypertension.

Both essential hypertension and the development of left ventricular hypertrophy are multifactorial. Several types of hypertrophy may develop. There is evidence that different agents used to treat hypertension may cause varying degrees of regression of left ventricular hypertrophy. In many instances in which regression of left ventricular hypertrophy has occurred in human subjects, there has been an associated improvement in echocardiographic evidence of ventricular function. Although most current evidence suggests that therapy should aim at both the control of blood pressure and the regression of left ventricular hypertrophy, one should be aware that an individual who is successfully treated for hypertension with a regimen that also produces regression of the compensatory left ventricular hypertrophy may be more susceptible to left ventricular failure if the severe hypertension should ever recur from whatever cause.

Cardiomegaly↗
PubMed2005

Evaluation of the cardiac isoform of alpha2-macroglobulin as a factor inducing cardiac hypertrophy.

Earlier studies from our laboratory showed that a 182-kDa high-molecular-weight protein appeared during early stages of development of cardiac hypertrophy in animals subjected to aortic constriction. Later it was confirmed that this protein is a cardiac isoform of alpha2-macroglobulin belonging to the macroglobulin family. Furthermore, it has been demonstrated that direct injection of the purified 182-kDa protein intravenously (through the tail vein) into the normal animals led to the development of cardiac hypertrophy. It was accompanied by enlargement of cardiac myocytes and induction of beta-myosin heavy chain (MHC) and MLC-2 gene expression. Multiple injections of 182-kDa protein-specific polyclonal antibody into the circulation of aorta-constricted animals completely abolished the development of hypertrophy and downregulated the expression of beta-MHC and myosin light chain (MLC)-2. The full-length cDNA of the 182-kDa protein cloned in eukaryotic expression vector, namely, pcDNA 3.1(-) could induce cardiac hypertrophy upon direct injection into rat heart. Hypertrophy was monitored by determining the heart weight/body weight ratio and also by Northern blot analysis of muscle-specific marker genes such as beta-MHC, MLC-2, and antrial natriuretic factor. Also, induction of promoter activity of beta-MHC and c-fos genes analyzed by chloramphenicol acetyl transferase assay confirmed the induction of cardiac hypertrophy upon direct injection of the full-length cDNA of the 182-kDa protein.

Animals↗
PubMed2002

Molecular and cellular mechanisms of mechanical stress-induced cardiac hypertrophy.

Congestive heart failure is one of the major issues for cardiologists. Since cardiac hypertrophy deteriorates into heart failure, it is important to elucidate the mechanisms of cardiac hypertrophy. Hemodynamic overload, namely mechanical stress, is a major cause for cardiac hypertrophy. Mechanical stress induces various hypertrophic responses such as activation of phosphorylation cascades of many protein kinases, expression of specific genes and an increase in protein synthesis. During this process, secretion and production of vasoactive peptides such as angiotensin II and endothelin-1, are increased and play critical roles in the induction of these hypertrophic responses. Recently, a Ca2+ dependent protein kinase, CaMK, and a Ca2+ dependent protein phosphatase, calcineurin, have attracted great attention as critical molecules that induce cardiac hypertrophy. In this review, we described the mechanisms by which mechanical stress induces cardiac hypertrophy, especially focusing on the role of calcineurin in the development of cardiac hypertrophy.

Angiotensin II↗
PubMed1982

Morphometric analysis of cardiac hypertrophy: left ventricular shape and number of muscle-fiber layers across left ventricular wall.

Left ventricular hypertrophy was quantitatively analysed in reference to the relation of ventricular shape and intramyocardial muscle-fiber arrangement. The shape of the ventricle was defined by VL/WL, left ventricular capacity ratio. The ratio was depressed in concentric hypertrophy due to pressure overload and elevated in eccentric hypertrophy due to volume overload. Moreover, VL/WL was reversely correlated with Nf, number of muscle-fiber layers across the left ventricular wall. The results supported the following view on the morphogenesis of left ventricular hypertrophy: The muscle fibers show the strained piling vertically across the ventricular wall to cause wall thickening and cavity narrowing in concentric hypertrophy. On the other hand, the muscle fibers are piled strongly in parallel to the ventricular surface in eccentric hypertrophy to result in attenuation of the wall thickness and dilatation of the ventricular cavity.

Adult↗
PubMed2006

Porphyromonas gingivalis-induced cellular hypertrophy and MMP-9 activity via different signaling pathways in H9c2 cardiomyoblast cells.

BACKGROUND: Little is known about the pathogenesis of cardiomyocyte hypertrophy caused by periodontitis pathogens. The purpose of this study was to determine the effect of the periodontal pathogen Porphyromonas gingivalis on cardiomyocyte hypertrophy. METHODS: Matrix metalloproteinase (MMP)-2 and MMP-9 activities and cellular morphology were measured by gelatin zymography and immunofluorescence after P. gingivalis-medium treatment with or without SB203580 (p38 mitogen-activated protein kinase cascade [p38] inhibitor), U0126 (mitogen-activated protein kinase kinase [MAPKK] inhibitor), LY294002 (phosphoinositide 3-kinase [PI3K] inhibitor), cyclosporin A (CsA; calcineurin inhibitor), SP600125 (c-Jun N-terminal kinase [JNK] inhibitor), proinflammatory interleukin (IL)-1, or anti-inflammatory IL-10 in cultured cardiomyoblast H9c2 cells. RESULTS: P. gingivalis medium increased MMP-9 activities and cellular sizes (+87%) of H9c2 cells, whereas Actinobacillus actinomycetemcomitans medium and Prevotella intermedia medium had no effects. The increased activity of MMP-9 treated with P. gingivalis medium was not mediated through p38, extracellular-regulated kinase (ERK), PI3K, calcineurin, and JNK signaling pathways and was not inhibited by IL-10. However, the hypertrophy of H9c2 cells induced with P. gingivalis medium was reduced by administration of SB203580 (-37%), U0126 (-35%), LY294002 (-49%), CsA (-49%), and SP600125 (-24%). CONCLUSIONS: Our findings suggest that P. gingivalis medium elevated MMP-9 activity and induced cardiomyoblast hypertrophy. However, P. gingivalis-induced H9c2 cell hypertrophy was mediated through p38, ERK, PI3K, calcineurin, and JNK signaling pathways, which are in a totally different regulatory pathway from P. gingivalis-elevated MMP-9 activity. These findings provide evidence that P. gingivalis infection activated multiple factors via different pathways to induce the development of hypertrophy of H9c2 cardiomyoblast cells.

Calcineurin↗
PubMed1988

Factors involved in the pathogenesis of hypertensive cardiovascular hypertrophy. A review.

All tissues can rapidly adapt their structural design whenever prolonged changes of load/activity occur within the limits characteristic of each tissue. This structural adaptation, however, is modified by various genetic and trophic influences. When antihypertensive therapy is considered in the hypertensive patient, such changes are usually well established and the cardiovascular system is structurally adapted to maintain a higher pressure than normal. Increased blood pressure and afterload cannot solely explain the development of cardiac hypertrophy. Permissive actions from the sympathetic nervous system and the circulating angiotensin II are likely, but conflicting results still exist. There is evidence for a functional renin-angiotensin system in the heart, which may be involved in the genesis of left ventricular hypertrophy. Also, a soluble factor in the hypertrophied myocardium that stimulates protein synthesis may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension. Hypertrophy of both the large and smaller arterial vessels has been shown to follow the same general pattern of development and regression as in the heart. The vascular hypertrophy (predominantly of the media in the arterioles) can be considered as the ultimate structural factor behind the progression of hypertension independent of the initiating factor. A vicious circle with the increased resistance as the key factor can be identified. There are at least 3 possible initiating factors: a small rise in arterial pressure, an abnormal or reinforced response to pressure, or trophic/mitogenic stimuli acting directly on the vascular smooth muscle cell. The ultimate goal in the treatment of high blood pressure is to reduce hypertension-related morbidity and mortality. Normalisation of structural cardiovascular changes is also important and easier to evaluate in the individual. Understanding of the pathogenesis of structural adaptation may help in the selection of the best treatment.

Cardiomegaly↗
PubMed1998

[Modelling of myocardial hypertrophy in vitro for solving problems of medicinal correction].

The work has been done on primary heart culture from neonatal rat ventricle. Cardiomyocyte hypertrophy was modelled using noradrenaline (NA), angiotensin II (AII) and fetal serum, respectively. Cell hypertrophy of primary heart cultures was assessed by measuring the surface area, the scope of protein synthesis estimated by 3H-leucine autoradiography and the contents of nucleic acids in gallocyanin-chromalum stained cardiomyocytes. The structure of myofibrillar apparatus was studied by rhodamine-conjugated phalloidin and indirect immunofluorescence of muscle alpha-actinin. Treatment with 10(-6) M NA increased 3H-leucine incorporation in 9-day old heart culture by 42% without changing cell size. AII in a dose 1 microM stimulated protein synthesis activity by 1.3 fold and the surface area by 1.7 fold, both in 2- and 9-day old primary heart cultures. The maximum stimulation of cell hypertrophy was provided by the medium supplemented with fetal serum. RNA contents in the cytoplasm of cardiomyocytes increased by 7.8 fold and the myocardial cell size by 2.9 fold in serum-supplemented culture by 9 days of cultivation. In the medium with fetal serum, amounts of cardiomyocytes with tetraploid nuclei reached 33%, against 14% in control. Coculturing of myocardiocytes and fibroblasts rendered effects of fetal serum on the growth of myocardiocytes. Cultivation in the presence of 1 microM enalapril, an ACE inhibitor, suppressed the development of cardiac muscle cells hypertrophy. The effect of enalapril depended on the degree of cellular hypertrophy. Addition of 10 microM amiloride to the medium lowered the protein synthesis by 29% independently on the initial cellular hypertrophy.

Adrenergic alpha-Agonists↗
PubMed2000

Specific role of the extracellular signal-regulated kinase pathway in angiotensin II-induced cardiac hypertrophy in vitro.

Although MAP (mitogen-activated protein) kinases are implicated in cell proliferation and differentiation in many cell types, the role of MAP kinases in cardiac hypertrophy remains unclear. We examined the role of extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAP kinase in angiotensin II (Ang II)-induced hypertrophy compared with phenylephrine-induced hypertrophy in neonatal rat cardiac myocytes. Both Ang II and phenylephrine activated ERKs to a similar extent, whereas phenylephrine caused stronger and more sustained activation of JNK and p38 than Ang II. PD98059, a specific inhibitor of MAPK/ERK kinase (MEK),inhibited Ang II-induced, but not phenylephrine-induced, expression of atrial natriuretic factor (ANF) at both the mRNA and polypeptide levels. SB203580, a specific inhibitor of p38 and some JNK isoforms, did not show significant effects on ANF expression induced by Ang II or phenylephrine. Although PD98059 and dominant-negative MEK1 blocked Ang II-induced activation of the ANF promoter, SB203580 or dominant-negative MEK kinase 1 (MEKK1) showed no effect. Phenylephrine-induced ANF promoter activation was significantly inhibited by SB203580 and dominant-negative MEKK1, but not by PD98059 or dominant-negative MEK1. Dominant-negative Ras inhibited both ERK activation and ANF up-regulation by Ang II, whereas constitutively active forms of Ras and MEK were sufficient to activate the ANF promoter. Dominant-negative Ras also partly inhibited the phenylephrine-induced activation of ANF promoter. PD98059 did not affect other markers of Ang II-induced hypertrophy, such as skeletal alpha-actin and c-fos expression, increases in the rate of protein synthesis or rapid sarcomeric actin organization. These results suggest that Ang II uses ERK for ANF expression, whereas phenylephrine uses other pathways. The Ras/ERK pathway selectively mediates ANF expression in various phenotypes observed in Ang II-induced hypertrophy. The ERK pathway mediates an agonist-specific and phenotype-specific response in cardiac hypertrophy.

Angiotensin II↗
PubMed1999

Na+/Ca2+ exchange current in myocytes isolated from rat hypertrophied heart.

Effects of myocardial hypertrophy on the Na+/Ca2+ exchange current in isolated rat cardiac myocytes were investigated, using whole cell patch techniques. Goldblatt 2-kidney, one-clip technique was used to induce cardiomyocyte hypertrophy. The results demonstrated that the Ni(2+)-sensitive Na+/Ca2+ exchange current density was larger in hypertrophied cells than that in normal cells. At a holding potential of mV, the outward current densities were 1.53 +/- 0.31 pA/pF in normal cells and 2.62 +/- 0.53 pA/pF in hypertrophied cells (P < 0.01). At a holding potential of -100 mV, the inward current densities were 0.42 +/- 0.14 pA/pF in normal cells and 1.12 +/- 0.33 pA/pF in hypertrophied cells (P < 0.001). The results suggest that during myocardial hypertrophy the Na+/Ca2+ exchange current is significantly increased.

Animals↗
PubMed1978

Evaluation of chamber and myocardial compliance in pressure overload hypertrophy.

The effect of pressure overload hypertrophy on isolated myocardial muscle preparations remains controversial. Moreover, the ultimate effect on the diastolic function of the left ventricle in the pressure overload states of man and the relative changes in chamber and myocardial stiffness remain incompletely studied. We review here the methods as well as results of dynamic diastolic stiffness analysis in 18 patients with valvular aortic stenosis and 5 normal subjects based upon the pressure-volume and circumferential stress-strain relations obtained by simultaneous left ventricular micromanometry and high-speed cineangiography. In addition, complementary analysis of dynamic diastolic stiffness findings in chronically instrumented animals, before and after the induction of hypertrophy, are reviewed. Increased diastolic intracavitary pressures during concentric hypertrophy were found to be attributable to both increased muscle mass as well as enhanced myocardial stiffness. However, both chamber and myocardial stiffness changes during hypertrophy were quite variable with some patients (and 2 of 6 dogs) showing no enhancement of stiffness parameters. In the chronically instrumented animals where dynamic, instantaneous stiffness changes and strain rates are more readily studied than in man, viscous (velocity dependent) effects were noted to be enhanced during hypertrophy. It is postulated that variable increases in diastolic stiffness during concentric hypertrophy in the intact heart results from varying degrees of myofiber architectural distortion and/or inconstant collagen content, and further correlative studies of morphology and mechanical function are needed.

Animals↗
PubMed2004

[Protective effect of berberine on cardiac hypertrophy induced by L-thyroxine in rats].

OBJECTIVE: To assess the effects of berberine on cardiac hypertrophy induceded by L-thyroxine(L-Thy) in rats. METHODS: A cardiac hypertrophy model was produced by intraperitoneal (i.p.) injection of L-thyroxine 0.5 mg/(kg.d) x 10 d. 24 SD rats were divided into three groups: 1. control (normal saline); 2. L-Thy; 3. i.p. L-Thy + berberine gastrogavage 30 mg/(kg.d) x 10 d. Then the cardiac indexes, Na(+)-K(+)-ATPase activity, Ca(2+)-ATPase activity, the cardiac nitric oxide (NO) content, and the CaN activity were measured. RESULTS: Compared with the measurements in the control group, the cardiac indexes and the CaN activity were remarkably increased in the hypertrophy group (P < 0.01), but the cardiac NO content, Na(+)-K(+)-ATPase activity and Ca(2+)-ATPase activity in myocardium were significantly decreased (P < 0.01). Further comparison between the hypertrophy group and the L-Thy + berberine group showed that berberine 30 mg/(kg.d) x 10 d prevented the ventricular hypertrophy induced by L-Thy and decreased the cardiac indexes and CaN activity (P < 0.01); berberine elevated the cardiac NO content, Na(+)-K(+)-ATPase activity and Ca(2+)-ATPase activity (P < 0.01). CONCLUSION: Berberine can prevent the cardiac hypertrophy induced by L-thyroxine in rats.

Animals↗