Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy

1982 ◽  
Vol 242 (5) ◽  
pp. H882-H889 ◽  
Author(s):  
J. M. Capasso ◽  
J. E. Strobeck ◽  
A. Malhotra ◽  
J. Scheuer ◽  
E. H. Sonnenblick
Keyword(s):  
Myocardial Hypertrophy ◽  
Applied Pressure ◽  
Pressure Overload ◽  
Heart Weight ◽  
Biochemical Alterations ◽  
Time To Peak ◽  
Velocity Of Shortening ◽  
Significant Depression ◽  
Contractile Performance ◽  
Biochemical Abnormalities

The effects of renovascular hypertension and its reversal on the contractile performance of papillary muscles from rats has been examined. Hypertension of 10 wk duration caused a 48% increase in heart weight and significant prolongations of isometric time to peak tension (TPT), time to half relaxation, and time to peak shortening (TPS). A significant depression in the velocity of shortening was observed in the 10-wk group. However, muscles from hypertensive rats were still able to maintain normal levels of peak isometric developed tension and peak shortening; this may be due to the observed prolongation of TPT and TPS, respectively. In addition, calcium-activated actomyosin ATPase activity was depressed in hearts of hypertensive animals. Reversal of hypertension was studied at 20 wk after the onset of hypertension (10 wk of hypertension followed by 10 wk of normotension). Contractile and biochemical alterations observed in hypertensive animals were reversed in rats undergoing this regime. Thus reversal of a gradually applied pressure overload resulted in the regression of mechanical and biochemical abnormalities associated with the pressure overload myocardial hypertrophy.

Abstract P056: RalGDS-Dependent Cardiomyocyte Autophagy in Load-Induced Ventricular Hypertrophy

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Oktay F Rifki ◽  
Brian O Bodemann ◽  
Michael A White ◽  
Joseph A Hill
Keyword(s):  
Membrane Trafficking ◽  
Pressure Overload ◽  
Small Gtpases ◽  
Heart Weight ◽  
Critical Feature ◽  
Mtor Inhibition ◽  
Hypertrophic Growth ◽  
Neonatal Cardiomyocytes ◽  
Cardiomyocyte Autophagy ◽  
Contractile Performance

Background: Recent work has demonstrated that autophagy, a phylogenetically conserved, lysosome-mediated pathway of protein degradation, is a key participant in pathological cardiac remodeling. One common feature of cell growth and autophagy is membrane biogenesis and processing. The exocyst, an octomeric protein complex involved in vesicle trafficking, is implicated in numerous cellular processes, yet its role in cardiomyocyte plasticity is unknown. Here, we set out to explore the role of small G protein-dependent membrane trafficking in stress-induced cardiomyocyte remodeling and autophagy. Methods and Results: Hearts from mice lacking RalGDS ( Ralgds -/- ), a guanine exchange factor (GEF) for the Ral family of small GTPases, were similar to wild-type (WT) littermates in terms of ventricular structure, contractile performance, and gene expression. However, Ralgds -/- hearts manifested a blunted growth response (p<0.05) to TAC-mediated pressure-overload stress as determined by heart weight to body weight ratios (HW/BW; WT, sham: 5.00 ± 0.21 mg/g, n=9; TAC: 6.93 ± 0.29, n=13; Ralgds -/- sham: 4.87 ± 0.19, n=6, TAC: 5.86 ± 0.10, n=6). Ventricular chamber size and contractile performance were unchanged in response to TAC in both genotypes. Interestingly, TAC-induced activation of the fetal gene program was similar in both genotypes despite the relative lack of hypertrophic growth in mutant hearts. Ralgds -/- mice also exhibited diminished load-induced cardiomyocyte autophagy. Consistent with the TAC findings, Ralgds -/- mice manifested a blunted autophagic response to 24-hour fasting, suggesting a generalized defect in autophagy. To explore underlying mechanisms, we tested in cultured neonatal cardiomyocytes two isoforms of Ral that are downstream of RalGDS (RalA, RalB) and whose actions are mediated by the exocyst. In these experiments, mTOR inhibition was maintained in response to starvation and rapamycin despite RalA or RalB knockdown; however, autophagy was diminished only in NRCM's with RalB knockdown, implicating RalB as required for cardiomyocyte autophagy. Conclusions: Together, these data implicate RalGDS-mediated induction of autophagy as a critical feature of load-induced cardiac hypertrophy.

Myocardial mechanical alterations during gradual onset long-term hypertension in rats

1981 ◽  
Vol 241 (3) ◽  
pp. H435-H441 ◽  
Author(s):  
J. M. Capasso ◽  
J. E. Strobeck ◽  
E. H. Sonnenblick
Keyword(s):  
Blood Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Left Renal Artery ◽  
Ventricular Performance ◽  
Time To Peak ◽  
Gradual Onset ◽  
Significant Depression ◽  
Female Wistar Rats

Although a suddenly produced load leads to depressed myocardial contractility, the effects of a slowly induced physiological overload have not been defined. Therefore, a more gradual pressure overload was produced in female Wistar rats by hypertension due to constriction of the left renal artery. Hypertension (systolic blood pressure greater than or equal to 150 mmHg) developed within 3 wk, and blood pressure continued to increase for the next 5 wk. Heart weights in hypertensive animals were elevated by 34% after the onset of hypertension. Isometric and isotonic contractions from left ventricular papillary muscles were recorded at 5, 10, 20, and 30 wk after the onset of hypertension. Total and actively developed isometric tension at all initial muscle lengths were significantly greater in hypertensive animals throughout the 30-wk period. Time to peak tension and time to half relaxation were significantly prolonged. Force-velocity curves demonstrated a significant depression in velocity of shortening at all relative loads in hypertensive muscles that progressed with the duration of hypertension. These studies suggest that myocardial hypertrophy may impart the ability to maintain ventricular performance in terms of force development while speed of shortening decays.

scholarly journals Impacts of a Specific Cyclooxygenase-2 Inhibitor on Pressure Overload–Induced Myocardial Hypertrophy in Rats

2019 ◽  
Vol 22 (6) ◽  
pp. E432-E437
Author(s):  
Zhixiang Xie ◽  
Shuyin Wang ◽  
Zijing Liang ◽  
Liangbo Zeng ◽  
Rongde Lai ◽  
...  
Keyword(s):  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cyclooxygenase 2 ◽  
Inflammatory Factors ◽  
Heart Weight ◽  
Sham Operation ◽  
Surgery Group ◽  
Tnf Α

Objective: The aim of this study was to observe the impacts of the specific cyclooxygenase-2 inhibitor celecoxib on cardiac structures, functions, and inflammatory factors during the process of pressure overload–induced myocardial hypertrophy. Methods: Twenty-four male Sprague Dawley rats were randomly divided into 3 groups: the sham operation group, the surgery group, and the celecoxib group. The model was established according to the abdominal aortic coarctation method. Results: At 16 weeks, rats in the celecoxib group were fed a celecoxib-mixed diet (10 mg/kg) for 8 consecutive weeks. At week 24 after model establishment, the cardiac structures and functions were observed; changes in the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), C-reactive protein (CRP), and uric acid (UA) were detected; and the contents of Smad1/2/3 proteins (Smad1, Smad2, and Smad3)  were determined. Left ventricular mass index, the heart weight/body weight ratio, and TNF-α, TGF-β, PGE2, CRP, and UA levels of the celecoxib group were all significantly decreased relative to those of the surgery group (P < .05); moreover, the cardiac functions were significantly improved compared to those of the surgery group (P < .05). Conclusions: These results show that inflammatory factors are involved in the myocardial hypertrophy process and that celecoxib may reverse myocardial hypertrophy through a variety of pathways.

Comparison of the contractile performance of the hypertrophied myocardium from spontaneous hypertensive rats and normotensive infarcted rats

1998 ◽  
Vol 76 (4) ◽  
pp. 387-394 ◽  
Author(s):  
J G Mill ◽  
MAS Novaes ◽  
M Galon ◽  
J B Nogueira ◽  
D V Vassallo
Keyword(s):  
Myocardial Infarction ◽  
Sarcoplasmic Reticulum ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Parallel Increase ◽  
Contractile Performance

The sarcoplasmic reticulum (SR) exerts a key role on the excitation-contraction coupling process in the myocardium. Since the relation between the volume of cellular organelles, such as SR, and the sarcolemmal area of myocytes is not uniform in myocardial hypertrophy of different etiologies, we compared the contractile performances of hypertrophied left ventricular papillary muscles from rats with pressure overload and with volume overload. Hemodynamically compensated spontaneous hypertensive rats (SHR, 3 months old, systolic blood pressure = 189 ± 4 mmHg, n = 8) and Wistar rats with healed (30 days) myocardial infarction (MI, n = 7) produced by ligation of the left coronary artery were used. Results were compared with age-matched Wistar control (CON) rats (n = 13). Force (F), corrected to muscle cross-sectional area (g/mm2), and dF/dt were recorded in muscles contracting isometrically and stretched to Lmax. The inotropic response to increasing extracellular Ca2+ concentrations (1.25 to 5.0 mM) was compared in twitches (0.5 Hz) and during tetanic stimulation (5 Hz, 30 s) in the muscles treated with 1 µM ryanodine. F recorded in basal conditions (Ca = 1.25 mM, 0.5 Hz) in the CON group (1.34 ± 0.20 g/mm2) was higher (p < 0.05) than in the MI (0.73 ± 0.13 g/mm2) and lower (p < 0.05) than in the SHR group (2.08 ± 0.25 g/mm2). Similar differences between groups were also observed in relation to +dF/dt. Increasing extracellular Ca produced a parallel increase of F and +dF/dt in the three groups of muscles. Ryanodine treatment reduced F and +dF/dt in all groups and completely inhibited the development of force in post-rest contractions, indicating SR inhibition. SHR muscles were more sensitive to ryanodine than CON and MI (F decrease = 64 ± 7, 51 ± 5, and 22 ± 5%, respectively, p < 0.05). The tetanic tension (Ca = 1.25 mM) was similar in SHR and CON (0.82 ± 0.19 and 0.92 ± 0.18 g/mm2; p > 0.05) and depressed in the MI group (0.35 ± 0.12 g/mm2). These data suggest an increased participation of SR as source of activator Ca in the hypertrophied muscle of SHR. This adaptation likely contributes to maintain the normal cardiac function in hemodynamically compensated SHR, despite increasing afterload levels. This adaptation seems not to occur after MI, which may contribute to the depressed contractile performance of the left ventricular muscle surviving to infarction.Key words: myocardial contractility, myocardial hypertrophy, sarcoplasmic reticulum, myocardial infarction, hypertension.

scholarly journals Osteopontin Modulates Myocardial Hypertrophy in Response to Chronic Pressure Overload in Mice

Hypertension ◽  
2004 ◽  
Vol 44 (6) ◽  
pp. 826-831 ◽  
Author(s):  
Zhonglin Xie ◽  
Mahipal Singh ◽  
Krishna Singh
Keyword(s):  
Myocardial Hypertrophy ◽  
Pressure Overload

scholarly journals Interrelation between Exercise Heart Rate, Post-Run Systolic Blood Pressure, and Myocardial Structure in Distance Runners

2018 ◽  
Vol 3 (66) ◽  
Author(s):  
Tomas Venckūnas ◽  
Birutė Mažutaitienė ◽  
Arvydas Stasiulis
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Wall Thickness ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Exercise Heart Rate ◽  
Training Volume ◽  
Distance Runners ◽  
Myocardial Wall

Endurance running is an exercise practiced by athletes in many sports. Being benefi cial to health, it is also under-taken by a great number of non-athletic individuals. Rigorous endurance training frequently induces symmetric (i. e. both ventricular chamber dilation and wall thickening) myocardial hypertrophy, which is a physiological adapta-tion. Although distance running is a sport associated with haemodynamic volume rather than pressure overload, in addition to enlarged cardiac output, systolic arterial blood pressure also considerably increases during running. The extent of the cardiac hypertrophy was shown to be correlated with peak blood pressure measured during laboratory exercise. However, the predominant type of myocardial hypertrophy (the ratio between the myocardial wall thickness and chamber size) in endurance runners remains contradictory, and the majority of the responsible factors are still to be determined. The aim of this study was to determine possible correlations between post-run systolic blood pressure and myocardial hypertrophy in endurance runners.Standard transthoracic two-dimensional M-mode echocardiography was performed in white adult male distance runners (n = 49) of national level within four weeks of treadmill testing, which was a non-continuous incremental exercise test employed for the determination of the heart rate as well as post-exertional systolic blood pressure re-sponse. Runners’ training volume (evaluated as the average number of hours per week spent training averaged over the past four weeks) correlated (p < 0.05) positively with the left ventricular (LV) wall thickness but not with the cavity size or LV mass (p > 0.05). Training volume also positively correlated with systolic blood pressure response to exercise (p < 0.05), but negatively with submaximal exercise heart rate (p < 0.01). Post-run systolic blood pressure correlated positively with LV wall thickness and LV concentricity (namely, the ratio between the myocardial wall thick-ness and chamber size) (p < 0.05), but no signifi cant correlation of any of the LV size parameters with resting heart rate, blood pressure, or systolic blood pressure in 2 to 4 min during the recovery period was revealed. Submaximal and maximal heart rate correlated signifi cantly and negatively with LV wall thickness, LV mass, and systolic blood pressure measured immediately after running (p < 0.05).Training volume and post-run systolic blood pressure have been found to correlate positively with LV wall thickness and concentricity in white adult male distance runners. Negative correlation of exercise heart rate has been found with the post-exercise systolic blood pressure, LV wall thickness, and LV mass.Keywords: myocardial hypertrophy, pressure overload, echocardiography, athlete’s heart.

Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload

2003 ◽  
Vol 285 (3) ◽  
pp. H1261-H1269 ◽  
Author(s):  
Ping Hu ◽  
Dongfang Zhang ◽  
LeAnne Swenson ◽  
Gopa Chakrabarti ◽  
E. Dale Abel ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Insulin Signaling ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Tissue Growth ◽  
Cardiac Response ◽  
Heart Weight ◽  
Surgical Morbidity ◽  
Aortic Banding

We developed a minimally invasive method for producing left ventricular (LV) pressure overload in mice. With the use of this technique, we quickly and reproducibly banded the transverse aorta with low surgical morbidity and mortality. Minimally invasive transverse aortic banding (MTAB) acutely and chronically increased LV systolic pressure, increased heart weight-to-body weight ratio, and induced myocardial fibrosis. We used this technique to determine whether reduced insulin signaling in the heart altered the cardiac response to pressure overload. Mice with cardiac myocyte-restricted knockout of the insulin receptor (CIRKO) have smaller hearts than wild-type (WT) controls. Four weeks after MTAB, WT and CIRKO mice had comparably increased LV systolic pressure, increased cardiac mass, and induction of mRNA for β-myosin heavy chain and atrial natriuretic factor. However, CIRKO hearts were more dilated, had depressed LV systolic function by echocardiography, and had greater interstitial fibrosis than WT mice. Expression of connective tissue growth factor was increased in banded CIRKO hearts compared with WT hearts. Thus lack of insulin signaling in the heart accelerates the transition to a more decompensated state during cardiac pressure overload. The use of the MTAB approach should facilitate the study of the pathophysiology and treatment of pressure-overload hypertrophy.

Abstract 080: Eya4 Induces Hypertrophy Via Regulation Of p27kip1

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Tatjana Williams ◽  
Moritz Hundertmark ◽  
Peter Nordbeck ◽  
Sabine Voll ◽  
Melanie Muehlfelder ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Dominant Negative ◽  
Heart Weight ◽  
Dominant Negative Effect ◽  
Mutant Form ◽  
Cardiac Phenotype ◽  
Truncating Mutation

Introduction: E193, a truncating mutation in the transcription cofactor Eyes absent 4 (Eya4) causes hearing impairment followed by heart failure. Here we identified the Eya4 dependent molecular mechanisms leading to the cardiac phenotype in the E193 mutation. Methods and Results: First we showed in vitro that the cyclin-dependent kinase inhibitor protein p27kip1 is a direct target of Eya4/Six1 and is suppressed upon Eya4 overexpression, whereas E193 has a dominant negative effect, releasing Eya4 mediated suppression of p27. We next generated transgenic mice with cardiac specific constitutive overexpression of full-length Eya4 or the mutant form E193. While E193 transgenic mice developed age-dependent DCM, Eya4 mice displayed cardiac hypertrophy already under basal conditions as judged by increases in heart weight and cardiomyocyte cross-sectional areas along with increases in myocardial dimension and mass. These two distinct cardiac phenotypes were even more aggravated upon pressure overload suggesting Eya4 is a regulator of cardiac hypertrophy. We also observed that the activity of Casein Kinase 2-α and the phosphorylation status of HDAC2 were significantly upregulated in the Eya4 transgenic mice, while they were significantly reduced in E193 mice, under baseline conditions and pressure overload. We were also able to identify a new human mutation (E215) with a phenotype comparable to the one seen in E193 patients. Conclusion: Our results implicate that Eya4/Six1 regulates cardiac hypertrophic reactions via p27/CK2-α/HDAC2 and indicate that truncating mutations in Eya4 interfere with this newly established signalling pathway.

Exercise conditioning increases rat myocardial calcium uptake

1986 ◽  
Vol 60 (5) ◽  
pp. 1673-1679 ◽  
Author(s):  
S. N. Levine ◽  
G. T. Kinasewitz
Keyword(s):  
Body Weight ◽  
Sarcoplasmic Reticulum ◽  
Adrenergic Receptors ◽  
Calcium Uptake ◽  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Heart Weight ◽  
Scatchard Analysis ◽  
Body Weight Ratio ◽  
Female Wistar Rats

To investigate potential mechanisms underlying the enhanced myocardial performance consequent to exercise training, the adrenergic receptors of myocardial tissue and Ca2+ uptake into sarcoplasmic reticulum-enriched fractions from exercise conditioned animals were compared with that of sedentary controls. Female Wistar rats were exercised by swimming 30 min (5 days/wk) for 12 wk. Exercise conditioning was effective in producing myocardial hypertrophy, as reflected by an increase in heart weight (1.179 +/- 0.022 vs. 1.031 +/- 0.020 g, P less than 0.001) and heart weight-to-body weight ratio (3.29 +/- 0.06 vs. 2.77 +/- 0.05 X 10(-3), P less than 0.001) but no difference in body weight. Despite the myocardial hypertrophy, neither the affinity nor the density of the alpha 1-adrenergic receptors or the beta-adrenergic receptors determined by Scatchard analysis of the ligands [3H]prazosin and [3H]dihydroalprenolol were significantly different between the two groups. The basal Ca2+ uptake into the sarcoplasmic reticulum was also similar (9.90 +/- 0.97 vs. 9.04 +/- 0.75 nmol/mg protein/min), but the addition of calmodulin produced a significantly greater increment in Ca2+ uptake into sarcoplasmic reticulum from the exercised-conditioned animals (1.90 +/- 0.23 vs. 1.21 +/- 0.19 nmol/mg protein/min, P less than 0.03). The adenosine triphosphatase (ATPase) activities of the sarcoplasmic reticulum-enriched fractions of the two groups were similar. We conclude that exercise conditioning produces an enhancement of calmodulin-mediated calcium uptake that is independent of any effect on Ca2+-ATPase.

scholarly journals The Effects of 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone on Pressure Overload-Induced Cardiac Remodeling in Rats and the Endothelial Mechanisms Based on PGI2

2015 ◽  
Vol 36 (3) ◽  
pp. 1004-1014 ◽  
Author(s):  
Jianchun Huang ◽  
Xiaojun Tang ◽  
Xingmei Liang ◽  
Qingwei Wen ◽  
Shijun Zhang ◽  
...  
Keyword(s):  
Microvessel Density ◽  
Cardiac Remodeling ◽  
Sham Group ◽  
Cell Function ◽  
Colorimetric Method ◽  
Pressure Overload ◽  
Primary Objective ◽  
Heart Weight ◽  
Model Group ◽  
Endothelial Cell Function

Aim: The primary objective of this study was to study the effects of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on pressure overload-induced cardiac remodeling in rats, as well as the endothelial mechanisms based on PGI2. Methods: Six weeks following surgery, rats were divided randomly into the following groups: a sham group, a model group, an MHBFC 12 mg/kg/day group (MHBFC 12), an indomethacin 2 mg/kg/day group (Indo 2), and an Indo 2+ MHBFC 12 group. The MS 4000 organism signal system was used to record the rats' hemodynamic indices. Additionally, the heart weight was determined, and the cardiac remodeling index was calculated. HE and Masson's stains were utilized to perform histological analyses; the immunofluorescence was used to observe the microvessel density of myocardial tissue; the colorimetric method was used to determine the hydroxyproline content of cardiac tissue; the ELISA method was used to measure the plasma PGI2 content; and transmission electron microscopy was used to observe the ultrastructure of the myocardium. Results: A hyperdynamic circulation state, cardiac remodeling, decreased microvessel density and decreased plasma PGI2 content were each observed in the model group compared with the sham group, in which any changes in the above parameters were effectively reversed by MHBFC. Single-use Indo administration resulted in the progression of these pathophysiological changes; however, MHBFC prevented the worsening of these parameters. Conclusion: MHBFC significantly reverses pressure overload-induced cardiac remodeling, and its mechanism may partially contribute to the amelioration of endothelial cell function and the augmentation of PGI2 synthesis and secretion.

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