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PubMed2006

Dominant-negative c-Jun inhibits rat cardiac hypertrophy induced by angiotensin II and hypertension.

Cardiac activator protein-1 (AP-1), composed of c-Jun, is significantly activated by hypertension or angiotensin II (AngII). This study was undertaken to elucidate whether c-Jun could be the potential target for treatment of cardiac hypertrophy. We constructed recombinant adenovirus carrying dominant-negative mutant of c-Jun (Ad.DN-c-Jun). Using catheter-based technique of adenoviral gene transfer, we achieved global myocardial transduction of DN-c-Jun in rats, to specifically inhibit cardiac AP-1. (1) AngII (200 ng/kg/min) infusion in rats caused cardiac hypertrophy, increased cardiac p70S6 kinase activity by 1.3-fold (P<0.05) and enhanced the gene expression of cardiac hypertrophic markers. Ad.DN-c-Jun, which was transferred to the heart 2 days before AngII infusion, prevented cardiac hypertrophy (P<0.01), decreased p70S6 kinase phosphorylation (P<0.05), and suppressed cardiac gene expression of brain natriuretic peptide, collagen I, III, and IV, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) (P<0.01). (2) In genetically hypertensive rats with cardiac hypertrophy, cardiac gene transfer of Ad.DN-c-Jun, without affecting hypertension, regressed cardiac hypertrophy (P<0.05), and suppressed p70S6 kinase phosphorylation by 20% (P<0.05) and suppressed the enhanced expression of collagen I, III, and IV, MCP-1 and PAI-1. These results provided the first evidence that in vivo blockade of cardiac c-Jun inhibits pathologic cardiac hypertrophy.

Adenoviridae↗
PubMed2005

Glucosamine induces cell-cycle arrest and hypertrophy of mesangial cells: implication of gangliosides.

Alterations in proliferation and hypertrophy of renal mesangial cells are typical features of diabetic nephropathy. The HP (hexosamine pathway) has been proposed as a biochemical hypothesis to explain microvascular alterations due to diabetic nephropathy; however, involvement of HP in the regulation of mesangial cell growth or hypertrophy has been poorly studied. Although gangliosides are known to regulate cell proliferation, their potential role in mesangial cell-growth perturbations has hardly been explored. In the present study, we investigated the effects of the HP activation, mimicked by GlcN (glucosamine) treatment, on mesangial cell growth and hypertrophy and the potential implication of gangliosides in these processes. Our results indicate that GlcN induced hypertrophy of mesangial cells, as measured by an increase in the protein/cell ratio, and it caused cell-cycle arrest by an increase in the expression of cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Furthermore, GlcN treatment resulted in a massive increase in the levels of gangliosides G(M2) and G(M1). Treatment of cells with exogenous G(M2) and G(M1) reproduced the effects of 0.5 mM GlcN on p21(Waf1/Cip1) expression, cell-cycle arrest and hypertrophy, suggesting that gangliosides G(M2) and G(M1) are probably involved in mediating GlcN effects. These results document a new role of the HP in the regulation of mesangial cell growth and hypertrophy. They also suggest a potential new mechanism of action of the HP through modulation of ganglioside levels.

Animals↗
PubMed2000

Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling.

Angiotensin II (AII) is a major determinant of arterial pressure and volume homeostasis, mainly because of its vascular action via the AII type 1 receptor (AT1R). AII has also been implicated in the development of cardiac hypertrophy because angiotensin I-converting enzyme inhibitors and AT1R antagonists prevent or regress ventricular hypertrophy in animal models and in human. However, because these treatments impede the action of AII at cardiac as well as vascular levels, and reduce blood pressure, it has been difficult to determine whether AII action on the heart is direct or a consequence of pressure-overload. To determine whether AII can induce cardiac hypertrophy directly via myocardial AT1R in the absence of vascular changes, transgenic mice overexpressing the human AT1R under the control of the mouse alpha-myosin heavy chain promoter were generated. Cardiomyocyte-specific overexpression of AT1R induced, in basal conditions, morphologic changes of myocytes and nonmyocytes that mimic those observed during the development of cardiac hypertrophy in human and in other mammals. These mice displayed significant cardiac hypertrophy and remodeling with increased expression of ventricular atrial natriuretic factor and interstitial collagen deposition and died prematurely of heart failure. Neither the systolic blood pressure nor the heart rate were changed. The data demonstrate a direct myocardial role for AII in the development of cardiac hypertrophy and failure and provide a useful model to elucidate the mechanisms of action of AII in the pathogenesis of cardiac diseases.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed2001

The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival.

Cardiac hypertrophy is a complex process involving the coordinated actions of many genes. In a high throughput screen designed to identify transcripts that are actively translated during cardiac hypertrophy, we identified a number of genes with established links to hypertrophy, including those coding for Sp3, c-Jun, annexin II, cathepsin B, and HB-EGF, thus showing the general utility of the screen. Focusing on a candidate transcript that has not been previously linked to hypertrophy, we found that protein levels of the tumor suppressor PTEN (phosphatase and tensin homologue on chromosome ten) were increased in the absence of increased messenger RNA levels. Increased PTEN expression by recombinant adenovirus in cultured neonatal rat primary cardiomyocytes caused cardiomyocyte apoptosis as evidenced by increased caspase-3 activity and cleaved poly(A)DP-ribose polymerase. Expression of PTEN was also able to block growth factor signaling through the phosphatidylinositol 3,4,5-triphosphate pathway. Surprisingly, expression of a catalytically inactive PTEN mutant led to cardiomyocyte hypertrophy, with increased protein synthesis, cell surface area, and atrial natriuretic factor expression. This hypertrophy was accompanied by an increase in Akt activity and improved cell viability in culture.

Animals↗
PubMed2004

Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure.

Cardiac hypertrophy and ensuing heart failure are among the most common causes of mortality worldwide, yet the triggering mechanisms for progression of hypertrophy to failure are not fully understood. Tissue homeostasis depends on proper relationships between cell proliferation, differentiation, and death and any imbalance between them results in compromised cardiac function. Recently, we developed a transgenic (Tg) mouse model that overexpress myotrophin (a 12-kDa protein that stimulates myocyte growth) in heart resulting in hypertrophy that progresses to heart failure. This provided us an appropriate model to study the disease process at any point from initiation of hypertrophy end-stage heart failure. We studied detailed apoptotic signaling and regenerative pathways and found that the Tg mouse heart undergoes myocyte loss and regeneration, but only at a late stage (during transition to heart failure). Several apoptotic genes were up-regulated in 9-month-old Tg hearts compared with age-matched wild type or 4-week-old Tg hearts. Cardiac cell death during heart failure involved activation of Fas, tumor necrosis factor-alpha, and caspases 9, 8, and 3 and poly(ADP-ribose) polymerase cleavage. Tg mice with hypertrophy associated with compromised function showed significant up-regulation of cyclins,cyclin-dependent kinases (Cdks), and cell regeneration markers in myocytes. Furthermore, in human failing and nonfailing hearts, similar observations were documented including induction of active caspase 3 and Ki-67 proteins in dilated cardiomyopathic myocytes. Taken together, our data suggest that the stress of extensive myocardial damage from longstanding hypertrophy may cause myocytes to reenter the cell cycle. We demonstrate, for the first time in an animal model, that cell death and regeneration occur simultaneously in myocytes during end-stage heart failure, a phenomenon not observed at the onset of the disease process.

Animals↗
PubMed2005

Losartan but not atenolol reduce carotid artery hypertrophy in essential hypertension. A LIFE substudy.

BACKGROUND: We wanted to investigate whether treatment with losartan, an angiotensin II receptor blocker, induced regression of carotid artery hypertrophy as compared to the beta-receptor blocker, atenolol. METHODS: In 45 patients recruited for the LIFE Study with stage II-III hypertension and ECG left ventricular (LV) hypertrophy, we measured blood pressure, intima-media thickness (IMT) and lumen in the common carotid arteries by ultrasound, and minimal forearm vascular resistance (MFVR) by plethysmography, after 2 weeks of placebo treatment and after 1, 2 and 3 years of anti-hypertensive treatment with either atenolol- or losartan-based regimens. We measured the same parameters in 26 normal subjects matched for age and gender. RESULTS: The patients had as compared to normotensive controls higher IMT (0.87 vs 0.76 mm, p = 0.001) and intima-media cross-sectional area (IMA) (19.7 vs 15.5 mm2, p<0.001). Systolic and diastolic blood pressures were reduced to the same degree in patients treated with losartan as compared to atenolol. However, IMA decreased significantly only in patients treated with losartan (19.2 vs 17.6 mm2, p = 0.001) and the average relative decrease in IMA during the 3 years of treatment was significantly higher in patients treated with losartan as compared to atenolol (-7.4 vs -2.0%, p<0.05). CONCLUSION: Patients with hypertension and LV hypertrophy had hypertrophy of the common carotid arteries. Losartan, but not atenolol, induced regression of this hypertrophy. Because carotid artery hypertrophy has been associated with strokes, our findings may explain the lower incidence of strokes in the LIFE study in patients treated with losartan as compared to atenolol.

Aged↗
PubMed1992

Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart. Mediation by the AT1 receptor.

Angiotensin II (AII) has been reported to have direct hypertrophic actions in mammalian and avian myocardium. In this study we determined whether AII had receptor-mediated effects on stimulating cardiac hypertrophy independent of mechanical stimuli (increased cardiac afterload) in adult rats. Angiotensin II was infused into Sprague-Dawley rats for 7 and 14 days. Following this infusion, left ventricular mass indexed to body weight (LV/BW) increased 18.6 and 17.3%, respectively, compared with control (saline infused) rats. Administration of the nonpeptide AII receptor antagonist Dup 753 prevented the increase in left ventricular hypertrophy. Blockade of converting enzyme with enalapril maleate and treatment with a vasodilator had no effect on the AII-induced hypertrophy. In this animal model, the cardiac hypertrophy appeared to be independent of cardiac afterload, because normalization of blood pressure with hydralazine did not prevent the AII-induced hypertrophy. These in vivo studies indicate that AII-induced cardiac hypertrophy is mediated through AT1 angiotensin receptors.

Angiotensin II↗
PubMed1977

Role of cardiac contractility in hypertrophy from chronic volume loading.

In an experimental model of chronic cardiac volume overloading, ie chronic A-V block, evaluations of cardiac function were performed during the phase of the development of hypertrophy (one and two weeks of A-V block) and at stable hypertrophy (ten weeks of A-V block). During a time period of ten weeks of volume overload left ventricular muscle mass increased to 1.41 of normal hearts. Cardiac performance measured from cardiac index, stroke volume, and left ventricular ejection fraction was not depressed at any evaluated state of hypertrophy. Normal cardiac performance was also demonstrated when the heart was stressed by high ventricular pacing rates. The contractile state of the intact heart was expressed as the velocity of the isometric left ventricular pressure rise (dP/dt) at comparable loading conditions. Increased dP/dtmax at a stage before stable hypertrophy was reached, even when preload is normalised by ventricular pacing (70/min) implies that the volume overloaded heart during the development of hypertrophy mobilises part of its contractile reserve. It is assumed that increased contractility is a functional cause of an increase in oxygen demand; and that an adequate energy availability is covered by the enlargement of the mitochondrial mass. At stable hypertrophy when the contractile material has also increased, a new steady state is reached and an again normal contractility indicates an also stable dynamic situation.

Animals↗
PubMed1986

Coronary vascular reserve in the greyhound with left ventricular hypertrophy.

The effects of physiological left ventricular hypertrophy on coronary reactivity and reserve were examined by comparing greyhounds with their remarkable myocardial hypertrophy with mongrel dogs (left ventricular body weight ratios 7.7(0.1) and 4.4(0.1) g X kg-1 respectively). Peak reactive hyperaemia and flow debt repayment after 15 s coronary occlusions were virtually identical in both groups at baseline heart rates and paced atrial rates up to 270 beats X min-1. Furthermore, the changes in myocardial blood flow and its transmural distribution after release of a 45 s coronary occlusion both at baseline heart rate and during atrial pacing at 210 beats X min-1 were similar in both greyhounds and mongrel dogs. Collateral flow during a 1 min coronary occlusion in conscious animals and myocardial flows and distribution during treadmill exercise were also similar. To determine minimal coronary vascular resistance intracoronary adenosine (400-600 micrograms X min-1) was infused to dilate maximally the coronary vasculature without having appreciable systemic effects. In both groups of dogs adenosine increased coronary flow six to seven fold. Coronary vascular resistance per gram of left ventricle decreased equally, and the minimal resistance was 2200(147) kPa X litre-1 X min X g (RU X g-1) in greyhounds and 2360(453) RU X g-1 in mongrels, thus indicating similar maximal vascularity in each gram of the hypertrophied and mongrel left ventricles. Because of the larger greyhound heart, the minimal coronary vascular resistance for the entire left ventricle (11.7(0.7)RU) was 50% of that in mongrel dogs (24.1(0.7)RU). Thus all forms of left ventricular hypertrophy cannot be assumed to have similar effects on the coronary vasculature. Whereas the pathological hypertrophy associated with renovascular hypertension and aortic banding is accompanied by decreased coronary vascularity, the myocardial hypertrophy of the greyhound is accompanied by increased total vascularity and preserved coronary reserve.

Adenosine↗
PubMed1990

31P magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure.

STUDY OBJECTIVE - The purpose of the study was to confirm the presence of abnormalities in the coronary vessels of hypertensive hearts, and to examine the effects of reduced coronary perfusion pressure. DESIGN - Rats were made hypertensive by aortic banding, after which coronary flow and myocardial energy metabolites were studied in isolated hearts at physiological (140 cm H2O) and reduced (80 cm H2O) coronary perfusion pressures and compared with normotensive controls. SUBJECTS - Wistar-Kyoto rats between 250 and 300 g were used. Left ventricular hypertrophy was generated by aortic banding in 29 rats; 8 were studied one week after banding, and 21 three weeks after banding. There were 45 controls. MEASUREMENTS and RESULTS - Energy metabolites were assessed using 31P magnetic resonance spectroscopy, standardised by high performance liquid chromatography of rapidly freeze clamped tissue. Left ventricular wall thickness was determined using two dimensional echocardiography. Coronary flow (normalised for heart weight) was reduced significantly after one and three weeks of left ventricular hypertrophy, and at either physiological or below physiological pressures. Hearts from aortic banded animals developed higher intraventricular pressure with reduced oxygen consumption when perfused at a physiological pressure, indicating increased thermodynamic efficiency. When perfused at reduced pressure, the developed pressure declined significantly in both the one week and the three week banded groups compared to normal hearts. The phosphorylation potential and intracellular pH (pHi) were not significantly lower after one week and three weeks of left ventricular hypertrophy when perfused at physiological pressure. When perfused at reduced pressure, phosphorylation potential declined significantly in both groups of hypertrophied hearts, whereas pHi declined significantly only in the three week hypertrophy group. CONCLUSIONS - There is improved thermodynamic efficiency of the hypertrophied myocardium when perfused at a physiological pressure, but when perfused at a reduced pressure, ventricular function, phosphorylation potential and pHi decline in rat hearts after three weeks of aortic constriction, indicating an impairment of coronary reserve.

Animals↗
PubMed1990

Compensated function in hypertrophied ventricles of Wistar Kyoto and spontaneously hypertensive rats.

STUDY OBJECTIVE: The aim of the study was to compare the compensatory nature of left ventricular hypertrophy in models of normal and increased peripheral resistance. DESIGN: Peak left ventricular performance was compared in normotensive Wistar Kyoto (WKY) rats, in a subset of this strain with biventricular hypertrophy associated with volume overload (WKY-CH), and in spontaneously hypertensive rats (SHR), all studied at one year of age (ie, long term hypertrophy). SUBJECTS: 8 WKY-CH rats with biventricular hypertrophy were compared with 8 WKY (normal right and left ventricular weights). These groups were then compared with 9 SHR rats. All were maintained under identical conditions. MEASUREMENTS AND MAIN RESULTS: Left ventricular to body weight ratios (mg:g) were as follows: WKY-CH 2.78(SEM 0.09); SHR 2.90(0.09); WKY 2.10(0.09). Systolic blood pressures (mm Hg) were normal in WKY-CH [104(9)] and WKY [111(9)], but raised in SHR [163(8)]. Left ventricles from WKY and WKY-CH had normal histology and no fibre disorientation, fibrosis, or other morphological abnormalities. Peak cardiac index (ml.min-1.body weight-1) measured during rapid volume expansion with Tyrode's solution was higher in WKY-CH [427(33)] than in WKY [315(33)] and SHR [349(31)] (p less than 0.05). When peak stroke volume was expressed per mg left ventricular weight there were no significant differences between the groups. Peripheral resistance (mean arterial pressure divided by cardiac output) at peak cardiac output was higher in SHR [1.20(0.12)] than in either WKY-CH [0.57(0.08)] or WKY [0.74(0.08)]. CONCLUSIONS: These data show that both types of hypertrophy enhance peak left ventricular performance. In WKY-CH, which have normal peripheral resistance, the larger ventricle allows a higher peak cardiac index compared to WKY with no left ventricular hypertrophy. In SHR, the higher left ventricular mass is used to overcome an increased peripheral resistance and thereby provide a normal peak cardiac index.

Animals↗
PubMed1990

Left ventricular hypertrophy sensitizes the myocardium to the development of ischaemia.

To evaluate the effects of left ventricular hypertrophy in the development of myocardial ischaemia as detected by thallium-201 exercise scintigraphy, we studied 150 patients by two-dimensional echocardiography, SPECT thallium-201 scintigraphy, and coronary arteriography. Patients were divided into four groups according to the presence or absence of left ventricular hypertrophy and coronary artery disease. There were 62 patients with coronary artery disease and 28 with left ventricular hypertrophy. Left ventricular mass index ranged from a mean of 91.2 g m-2 in the no LVH no CAD group, to a mean of 150.6 g m-2 in the LVH CAD group. For the whole group, the sensitivity of thallium for the detection of coronary artery disease was 82%, specificity 75%, positive predictive value 70%, and negative predictive value 86%. The proportion of patients with abnormal thallium was highest (100%) in the group with left ventricular hypertrophy and coronary artery disease. The second largest group with abnormal perfusion by thallium imaging comprised patients with coronary artery disease and no left ventricular hypertrophy (78%). Both coronary artery disease and left ventricular mass index were demonstrated to be independent predictors of myocardial ischaemia in a multivariate regression model (P = 0.01). We conclude that left ventricular hypertrophy sensitizes the myocardium for the development of ischaemia.

Adult↗
PubMed1984

The hypertrophied myocardium accumulates the MB-creatine kinase isozyme.

Myocardial hypertrophy was produced in the dog by volume overload, secondary to hypertension, and pressure overload to left or right ventricles and in the rat by pressure overload to the left or right ventricles, by elevating thyroxine-levels and secondary to spontaneous hypertension in order to test whether there are changes in the creatine kinase system in hypertrophied heart. Although there was little or no change in total creatine kinase activity, there were changes in the distribution of the creatine kinase isozymes. In the dog, a 4-10-fold increase in the tissue content of MB-creatine kinase was observed for heart chambers with a 40-90% increase in the ratio of ventricular weight to body weight. In the rat, MB-creatine kinase also accumulated in hypertrophied ventricles. For the spontaneously hypertensive rat, the correlation between increased fetal creatine kinase isozymes and increased ratio of ventricular weight to body weight was excellent (r approximately 0.92). During the transition from compensated hypertrophy to failure in the spontaneously hypertensive rat, there is a 50% decrease in mitochondrial creatine kinase activity. P-31 NMR magnetization transfer experiments suggest that flux through the creatine kinase reaction is 3-fold lower than normal in these failing hearts. These results show that there are changes in the distribution of the creatine kinase isozymes in hypertrophied heart and suggest that one of these changes characterizes compensated hypertrophy (increased fetal-type creatine kinase isozymes) while another characterizes the transition to failure (decreased mitochondrial creatine kinase).

Animals↗
PubMed1984

Gene expression in cardiac hypertrophy in rat and human heart muscle.

Changes in the cardiac contents of microsomal RNA and poly(A)-containing mRNA have been examined during induction and regression of heart muscle hypertrophy in rat hearts, as well as possible changes in the subcellular distribution and protein-synthetic activity of cardiac mRNA. In addition, cardiac biopsies from patients with mitral valve diseases were evaluated for their mRNA contents. Induction of heart muscle hypertrophy was accompanied by substantial increases in cardiac microsomal RNA (30-60%) and cardiac mRNA (20-80%). During regression of hypertrophy increased levels of cardiac microsomal RNA and mRNA returned to normal values within 10-16 days. In general, cardiac mRNA levels were lower in human heart muscle than in rat heart muscle. Since the subcellular distribution of the microsomal RNA and of the mRNA as well as the protein-synthetic activity of the mRNA were not changed in the hypertrophied animals as compared with normal animals, and since the cardiac contents of most specific cardiac mRNA species (mRNAs for MHC, MLC1 and MLC2, actin, tropomyosin, troponin-T, myoglobin) increased proportionately, it is concluded that during induction of hypertrophy activation of gene expression occurs and affects the genes coding for the major cardiac proteins to a similar extent. This does, however, not exclude the possibility of more specific shifts in isoprotein patterns and in the levels of their corresponding mRNAs. It is proposed that changes in cardiac mRNA levels are the major regulatory factor in causing changes in cardiac protein synthesis rates leading to the induction and regression of cardiac hypertrophy.

Animals↗
PubMed1984

Correlation of myosin isoenzyme alterations with myocardial function in physiologic and pathologic hypertrophy.

To explore the interactions of physiologic and pathologic hypertrophy, four groups of hearts were studied in an isolated working rat heart apparatus. Cardiac contractile proteins were also evaluated. The groups were hearts of female control sedentary rats; rats subjected to a 10-week swimming programme; rats with renal hypertension; and hypertensive rats subjected to a 10-week swimming programme. The swimming programme in normotensive female rats caused a 30% cardiac hypertrophy, in hypertensive animals 46% hypertrophy, and in combined hypertension and swimming 70% hypertrophy. Ca2+-myosin ATPase activity and actin-activated myosin ATPase were elevated in hearts of swimmers, depressed in hearts of hypertensive sedentary animals and similar to control values in hearts of hypertensive swimmers. Myosin V1 isoenzyme content was increased in hearts of swimmers, depressed in hearts of hypertensives, but normal in hearts of hypertensive swimmers. Reciprocal relationships were seen with the V3 isoenzyme. Stroke work, mean velocity of circumferential fibre shortening, and per cent fractional shortening at the midwall showed increased values for hearts of swimmers, depressed values for hearts of hypertensives, and normal values or values above the control for hearts of hypertensive swimmers. Myocardial flow measured with microspheres was increased in the left ventricle of swimmers, depressed in hearts of hypertensives and still depressed in hypertensive swimmers, but significantly higher than in the hypertensives alone. The correlation of actin-activated ATPase activity and of fractional shortening was linear among the four groups. These studies demonstrate that physiologic and pathologic hypertrophy in the rat have distinctly opposite effects on contractile proteins and contractile performance. When one type of hypertrophy is superimposed on the other the effects are additive.

Actins↗
PubMed2004

Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats.

Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determine if the increased cardiac ACE1 actively plays a role or is merely the consequence of pathological changes in the process of cardiac hypertrophy, we generated a transgenic rat model with selective over-expression of human ACE1 in the cardiac ventricles. The left ventricular ACE1 activity is elevated about 50-fold in transgenic rats. Angiotensin-1 perfusion of isolated hearts demonstrated a significant decrease in coronary artery flow compared with non-transgenic littermates, suggesting that the transgenic ACE1 is functional. Neither cardiac hypertrophy nor other morphological abnormalities were observed in transgenic rats under standard living conditions. It was found, however, after induction of hypertension by suprarenal aortic banding, that the degree of cardiac hypertrophy in transgenic rats was significantly higher than that of banded control rats. The expressions of both ANF and collagen III, molecular markers of cardiac hypertrophy, were also increased in banded transgenic rats compared with banded control. Our results suggest that increased cardiac ACE1 does not trigger but augments cardiac hypertrophy.

Angiotensin I↗
PubMed1990

Morphological quantification and differentiation of left ventricular hypertrophy in hypertrophic cardiomyopathy and hypertensive heart disease. A two dimensional echocardiographic study.

Differentiation between hypertrophic cardiomyopathy and hypertensive heart disease is a diagnostic challenge. M-mode echocardiography only permits assessment of hypertrophy in limited areas of the left ventricular wall. 2-D echocardiography allows visualization of most of the myocardium. To assess the reliability of conventional M-mode echocardiographic and 2-D echocardiographic criteria in patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HY), 30 patients with hypertrophic cardiomyopathy and 30 patients with hypertension and severe cardiac hypertrophy were examined using M-mode and 2-D echocardiography. Although the M-mode echocardiographic features showed statistically significant differences between the mean values in the two groups, the degree of overlap made the differentiation of the individual patients difficult. The diagnostic sensitivity and specificity of classic echocardiographic features were assessed: ventricular septal thickness greater than or equal to 1.5 cm, 90% and 43% (sensitivity and specificity, respectively); ventricular septal thickness to posterior wall ratio greater than or equal to 1.5, 83% and 56%; cross-sectional area at papillary level greater than 21 cm2m-2, 80% and 73%; septal segment of the myocardial ring at papillary level greater than 6.5 cm2m-2, 80% and 87%; and the combined criteria of cross-sectional area at papillary level greater than 21 cm2m-2 and septal segment greater than 6.5 cm2m-2, 77% and 93%. Quantitative 2-D echocardiography is useful to differentiate patients with hypertrophic cardiomyopathy from those with secondary myocardial hypertrophy due to hypertension. Hypertrophic cardiomyopathy is characterized by a spectrum of different morphological patterns of hypertrophy. Patients with the predominant region of hypertrophy in the anterolateral free wall or the apical region of the left ventricle were not detected with our quantitative method. Patients with this type of hypertrophy are relatively rare in the western population.

Adult↗
PubMed1987

Role of beta 1-adrenoceptors in hypertensive cardiac hypertrophy.

Experimental and clinical evidence indicates that cardiac hypertrophy in systemic hypertension may not simply result from the mechanical stress of increased afterload. Several lines of evidence suggest that sympathetic nervous influence stimulates cardiac growth. A previous study indicated that sympathetic tone may be important in the two-kidney, one-clip model of renovascular hypertension. Hence, we investigated the role of cardiac beta-receptors by testing the effects of the cardioselective beta-receptor blocker, atenolol, on regression and prevention of ventricular hypertrophy in this model. Renal hypertensive rats were assigned to a 'prevention' and a 'reversal' protocol, receiving the drug before or after the development of hypertension and cardiac hypertrophy. Untreated control animals developed severe hypertension (205 +/- 9 mmHg) and marked cardiac hypertrophy (heart weight/body weight ratio: 3.86 +/- 0.23 mg/g) when compared to sham-operated controls (129 +/- 1 mmHg and 2.38 +/- 0.06 mg/g, respectively). Atenolol (440 mg/kg per day) failed to prevent or reverse hypertension (213 +/- 5 and 194 +/- 11 mmHg) or cardiac hypertrophy (4.10 +/- 0.39 and 3.51 +/- 0.25 mg/g, respectively). Effective beta-blockade was verified by significantly lower heart rates in treated animals (382 +/- 10 and 368 +/- 9 beats/min, respectively) than untreated controls (486 +/- 28 beats/min; P less than 0.01). Similarly, plasma renin activity returned to baseline in atenolol-treated animals. Cardiac catecholamines were markedly decreased in hypertrophied hearts (significant only for norepinephrine) and remained unaffected by atenolol treatment. However, both the prevention and reversal protocol strikingly reduced mortality in hypertensive animals (0 and 14%, respectively, versus 57%; P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗