Effect of Berberine on Regression of Pressure-Overload Induced Cardiac Hypertrophy in Rats

2002 ◽  
Vol 30 (04) ◽  
pp. 589-599 ◽  
Author(s):  
Ying Hong ◽  
Siu-Chun Hui ◽  
Tak-Yuen Chan ◽  
Jia-Yu Hou
Keyword(s):  
Cardiac Hypertrophy ◽  
Matched Control ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Treated Group ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Left Ventricular Tissue ◽  
Ventricular Tissue ◽  
Contraction And Relaxation

Berberine is the basic chemical component of a Chinese herb, Coptis chinensis Franch (coptis), considered to be useful in treating some diseases of the cardiovascular system, such as hypertension and chronic heart failure (CHF). In this study, we investigate the inhibitory effect of berberine on experimental cardiac hypertrophy, which is regarded as a risk factor of CHF and other heart diseases. Forty-two male SD rats were divided into four groups: age-matched control, aortic banding model, berberine-treated group and captopril-treated group. Cardiac hypertrophy was induced by suprarenal abdominal aorta constriction (banding). The drugs were orally administered for 8 weeks starting from 4 weeks after surgery at dosage of berberine 10 mg/kg and captopril 50 mg/kg. Blood pressure (BP) was measured four times during the period of the experiment, and hemodynamic parameters, cardiac index, cell size of left ventricular myocardium and total protein of left ventricular tissue were detected 8 weeks after treatment with drugs. The data from the present study showed that: (1) The BP of the aorta banded rats was increased compared with those of the normal ( p < 0.001) and the age-matched control rats ( p < 0.001), and berberine showed no significant effect on it. (2) After 8 weeks of treatment with berberine, the elevated left ventricular end diastolic pressure (LVEDP) was slightly decreased compared with the aortic banded rats. Meanwhile, the maximum rates of contraction and relaxation (± dp/dt max) was increased ( p < 0.05) and the time to reach the point of maximum rate from beginning of contraction (t-dp/dt) was shortened ( p < 0.01), indicating that the functions of heart, both contraction and relaxation, were improved. (3) Cardiac growth was inhibited by treatment with berberine. Both whole heart and left ventricular weight were notably decreased compared with the banded rats ( p < 0.05 and p < 0.01). (4) The cell size of left ventricular myocardium was significantly reduced ( p < 0.001) and the total protein of left ventricular tissue was slightly down-regulated by treatment with berberine. These data suggest that berberine can improve abnormal cardiac function and can prevent the development of left ventricular hypertrophy induced by pressure overload. This indicates that it may have therapeutic potential in the treatment of CHF.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

P121 Pressure overload-induced functional and metabolic impairments in type 2 diabetic hearts are ameliorated by inhibition of xanthine oxidase

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
Y Igaki ◽  
M Tanno ◽  
H Kouzu ◽  
Y Tatekoshi ◽  
T Yano ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Xanthine Oxidase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Dependent Manner ◽  
Phenylephrine Infusion ◽  
Type 2 Diabetic

Abstract Funding Acknowledgements SANWA KAGAKU KENKYUSHO Co., Ltd. Background   We have recently demonstrated that AMP deaminase (AMPD) is upregulated in OLETF, obese type 2 diabetic (T2DM) rats, and that the upregulated AMPD contributes to depletion of myocardial ATP at the time of pressure overload, leading to diastolic dysfunction.  On the other hand, AMPD promotes the formation of IMP from AMP, and IMP is in turn further converted to hypoxanthine and xanthine, substrates of xanthine oxidase (XO), which produces uric acid with ROS as a byproduct.  Based on these findings, we tested the hypothesis that inhibition of XO ameliorates the pressure overload-induced diastolic dysfunction in T2DM rats.  Methods and results Metabolomic analyses of the left ventricular myocardium revealed that levels of myocardial hypoxanthine and xanthine were significantly higher by 30% and 28%, respectively, in OLETF than in LETO, non-diabetic control rats, under the condition of pressure overloading (200-230 mmHg) induced by phenylephrine infusion. Myocardial XO activity in OLETF was 57.9% higher than that in LETO, and the activity was significantly attenuated by oral administration of topiroxostat, an XO inhibitor, at 0.1-0.5 mg/kg/day for 14 days in a dose-dependent manner.  Pressure volume loop analyses showed that the pressure overloading induced by phenylephrine infusion resulted in significantly higher LVEDP in OLETF than in LETO (18.3 ± 1.5 vs. 12.2 ± 1.3 mmHg, p &lt; 0.05, n = 7), though LVEDPs at baseline were comparable in OLETF and LETO (5.6 ± 0.4 vs. 4.7 ± 0.7 mmHg).  Treatment with topiroxostat significantly suppressed the pressure overload-induced elevation of LVEDP in OLETF (18.3 ± 1.5 vs. 11.3 ± 1.1 mmHg, p &lt; 0.05) but not in LETO.  Tau, the time constant of LV pressure decay, was significantly prolonged to 14.7 ± 0.7 ms (p &lt; 0.05) by pressure overloading in OLETF but not in LETO, though baseline Tau values were similar in LETO and OLETF (6.1 ± 0.2 vs. 8.0 ± 0.4 ms).  The prolongation of Tau by pressure overloading in OLETF was significantly attenuated by treatment with topiroxostat.  Ea/Ees, an index for ventricular-arterial coupling, was higher in OLETF than in LETO (2.3 ± 0.3 vs. 1.6 ± 0.3, p &lt; 0.05) under the condition of pressure overloading, and it was also improved by topiroxostat in OLETF (1.2 ± 0.2, p &lt; 0.05).  Myocardial ATP content was lower in OLETF than in LETO under the condition of pressure overloading (2966 ± 400 vs. 1818 ± 171 nmol/g wet tissue, p &lt; 0.05), but treatment with topiroxostat significantly restored the ATP level (2629 ± 307 nmo/g wet tissue). Conclusion:  In T2DM hearts, not only XO activity but also XO substrates are upregulated and upregulated AMPD may be involved in the upregulation.  Inhibition of XO ameliorates pressure overload-induced diastolic dysfunction and improves ventricular-arterial coupling most likely through augmented ATP preservation.

scholarly journals The Effects of Aqueous Extract from Nardostachys chinensis Batalin on Blood Pressure and Cardiac Hypertrophy in Two-Kidney One-Clip Hypertensive Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Rayile Aisa ◽  
Zhaoxia Yu ◽  
Xiangyang Zhang ◽  
Dilinuer Maimaitiyiming ◽  
Lipeng Huang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Aqueous Extract ◽  
Caspase 3 ◽  
Left Ventricular ◽  
Left Renal Artery ◽  
Hypertensive Rats ◽  
Left Ventricular Tissue ◽  
Nardostachys Chinensis ◽  
Ventricular Tissue

Aims. The aim of this study was to investigate the effects of the aqueous extract of Nardostachys chinensis Batalin (NCBAE) on blood pressure and cardiac hypertrophy using two-kidney one-clip (2K1C) hypertensive rats. Methods. 2K1C rat models were set up by clipping the left renal artery. Sham-operated rats underwent the same surgical procedure except for renal arterial clipping. 2K1C hypertensive rats were orally given NCBAE at doses of 210, 420, and 630 mg·kg−1·d−1 for 6 weeks. Twelve weeks after surgery, rat SBP and echocardiographic parameters were measured, cardiac histopathology was assessed, serum NO and LDH were detected, and the expression of Bcl-2 and caspase-3 of left ventricular tissue was assessed by western blot. Results. Treatment with NCBAE resulted in a decrease of SBP, LVPWd, LVPWs, IVSd, IVSs, LVW/BW ratio, and cardiomyocyte CSA, an increase of LVEF, and inhibition of 2K1C-induced reduction in serum NO and elevation of LDH compared with 2K1C group. NCBAE intervention also showed a significant increase of Bcl-2 expression and reduction of cleaved caspase-3 level dose-dependently in left ventricular tissue. Conclusion. Our data demonstrate that NCBAE has an antihypertensive property and protective effect on 2K1C-induced cardiac hypertrophy especially at the dose of 630 mg·kg−1·d−1.

scholarly journals Transient Upregulation of Protein Kinase C in Pressure-Overloaded Neonatal Rat Myocardium

2010 ◽  
pp. 25-33 ◽  
Author(s):  
B Hamplová ◽  
F Novák ◽  
F Kolář
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Left Ventricular Myocardium ◽  
Aortic Constriction ◽  
Cardiac Growth ◽  
Kinase C

Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms α, δ and ε in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of 32P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (105 × g) and nuclear-cytoskeletalmyofilament-enriched (103 × g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the 3rd day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCδ, which increased significantly at d10 in the cytosolic fraction at the expense of the membraneenriched fraction. It is concluded that PKCα, PKCδ and PKCε undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.

scholarly journals Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats

2020 ◽  
Vol 319 (6) ◽  
pp. H1358-H1368
Author(s):  
Frederick M. Zasadny ◽  
Jhansi Dyavanapalli ◽  
N. Maritza Dowling ◽  
David Mendelowitz ◽  
Matthew W. Kay
Keyword(s):  
Heart Failure ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Cholinergic Neuron ◽  
Left Ventricular Myocardium ◽  
Cholinergic Stimulation ◽  
Neuron Activation ◽  
Therapeutic Outcomes ◽  
Insight Into

Analysis of electrophysiology from optical mapping of failing left ventricular myocardium provided insight into the possible therapeutic outcomes of cholinergic stimulation within the left ventricle. Chronic hypothalamic oxytocin neuron activation for downstream cardiac cholinergic neuron stimulation blunted onset of failing electrophysiology induced by pressure overload-induced heart failure in rats.

Inhibition of IκB phosphorylation prevents load-induced cardiac dysfunction in mice

2012 ◽  
Vol 303 (12) ◽  
pp. H1435-H1445 ◽  
Author(s):  
Tetsu Tanaka ◽  
Masahito Ogawa ◽  
Jun-ichi Suzuki ◽  
Asuka Sekinishi ◽  
Akiko Itai ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Dysfunction ◽  
Cardiac Fibrosis ◽  
Nuclear Translocation ◽  
Pressure Overload ◽  
Treated Group ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 2 ◽  
Cardiomyocyte Hypertrophy ◽  
Iκb Kinase

Pressure overload is known to be a cause of cardiac hypertrophy that often transits to heart failure. Although nuclear factor (NF)-κB is a key factor in the progression of cardiac hypertrophy, its pathophysiology is yet to be elucidated. Thus, we aimed to show that inhibition of NF-κB activation improves pressure overload-induced cardiac dysfunction. To assess the effect of inhibition on NF-κB activation in pressure overload cardiac hypertrophy, we used IMD-1041 in a murine thoracic aortic constriction (TAC) model. IMD-1041 inhibits the phosphorylation of IκB via inhibition of IκB kinase-β. IMD-1041 (100 mg·kg−1·day−1) or vehicle was administered orally into mice once a day, and mice were euthanized on day 42 after TAC. TAC resulted in left ventricular wall thickening, cardiac dysfunction, and increases of heart and lung weight, whereas IMD-1041 significantly suppressed the development of cardiac hypertropy 6 wk after TAC. Histologically, developed cardiac fibrosis and cardiomyocyte hypertrophy occurred in the vehicle-treated group, whereas IMD-1041 significantly attenuated these changes. IMD-1041 suppressed the expression of p65-positive cells and nuclear translocation of p65 induced by TAC compared with vehicle. Matrix metalloproteinase-2 activity increased in the vehicle + TAC-treated group; however, it was suppressed in the IMD-1041 + TAC-treated group. IMD-1041 treatment from day 28 to day 42 after TAC significantly attenuated the decrease in the percentage of fractional shortening and cardiac fibrosis without an antihypertrophic effect. In conclusion, IMD-1041 may be useful for preventing pressure overload-induced cardiac dysfunction and the transition of cardiac hypertrophy to contraction failure via suppression of NF-κB activation.

Microtubules are involved in early hypertrophic responses of myocardium during pressure overload

1998 ◽  
Vol 275 (2) ◽  
pp. H341-H348 ◽  
Author(s):  
Masaru Takahashi ◽  
Hiroyuki Tsutsui ◽  
Hirofumi Tagawa ◽  
Keiko Igarashi-Saito ◽  
Kyoko Imanaka-Yoshida ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Deuterium Oxide ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Contractile Protein ◽  
Similar Degree ◽  
Left Ventricular Myocardium ◽  
Mrna Levels ◽  
Rna Content

Mechanical overloading to cardiac muscle causes fetal contractile protein gene expression and acceleration of protein synthesis. Myocyte microtubules might be involved in these pressure overload-induced hypertrophic responses. We assessed c- fos and fetal contractile protein genes such as β-myosin heavy chain (MHC) and α-skeletal actin using Northern blot analysis and quantified total cardiac protein, DNA, and RNA content in the left ventricular myocardium obtained from four groups of rats: sham-operated rats; sham-operated rats treated with colchicine, which depolymerized microtubules; rats in which acute pressure overload was imposed by abdominal aortic constriction for 3 days (AoC); and AoC rats treated with colchicine (AoC + colchicine). Systolic arterial pressure was elevated to a similar degree in AoC and AoC + colchicine rats. c- fos and β-MHC mRNA levels were significantly upregulated in AoC rats, which was attenuated by microtubule inhibition. Both RNA content and RNA-to-DNA ratio, the index of the protein synthesis capacity, were increased in AoC rats, which effect was also abolished by colchicine. Furthermore, induction of nonfunctioning microtubules by taxol or deuterium oxide exerted the same inhibitory effects. Thus the hypertrophic responses of the myocardium during pressure overload might depend on the integrity of myocyte microtubules.

scholarly journals Evaluation of myocardial relaxation in conditions of cardiac remodeling

2009 ◽  
Vol 62 (11-12) ◽  
pp. 555-568 ◽  
Author(s):  
Nina Djukanovic ◽  
Vladimir Jakovljevic ◽  
Vujadin Mujovic
Keyword(s):  
Cardiac Remodeling ◽  
Arterial Wall ◽  
Age Groups ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Arterial Stenosis ◽  
Left Ventricular Myocardium ◽  
Cardiac Wall ◽  
Contraction And Relaxation

The term cardiodynamics refers to dynamic events associated with cardiac contraction and relaxation. The occurring wave of excitement spreads very quickly along the entire atrial musculature and after a brief AV retention it affects all muscle cells of the ventricles. Excitation, that is, the increase in action potentials, precedes the contraction of the myocardium, which follows the 'all or none' rule. Each contraction results in relaxation of the myocardium, so that the contraction and relaxation cycles continually follow each other in succession. The entire cardiodynamics, hemodinamics, i.e. signaling mechanisms of the heart are altered in the remodeling (alternation) condition of the left ventricular myocardium, i.e. the musculature and the whole arterial wall. Remodeling of the cardiac wall and layers of the arterial wall is a negative factor, because it leads to disturbances of the cardiac contraction and relaxation cycles and incites progression of the arterial hypertension, emergence of atherosclerosis and arterial stenosis. Today, the genetic base of the cardiac remodeling is the object of intensive studies. Cardiomyopathies are primary disorders of the myocardium associated with abnormalities of the cardiac wall thickness, the size of chambers, contractions, relaxations, signal conduct and rhythm. They are the major cause of morbidity and mortality for all age groups. Mechanisms of these events on the molecular level will be discussed in the following study.

scholarly journals MiR-139-3p is related to left ventricular hypertrophy and cardiomyocyte apoptosis in two-kidney one-clip hypertensive rats

2015 ◽  
Vol 67 (2) ◽  
pp. 427-435
Author(s):  
Xiaomin Yang ◽  
Hui Yu ◽  
Hai Hu ◽  
Jianwei Yue ◽  
Xuyang Tian ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Mitogen Activated Protein Kinase ◽  
Left Ventricular Myocardium ◽  
Hypertensive Rats ◽  
Mitogen Activated Protein

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in many physiological and pathological processes. Previous studies have reported the role of miR-139-3p in cancer. However, its specific roles and functions in the heart undergoing hypertrophy have yet to be fully elucidated. In the present study, a significant upregulation of miR-139-3p expression was demonstrated in the left ventricular myocardium of two-kidney one-clip (2K1C) hypertensive rats using microarray and quantitative real-time PCR (qRT-PCR). Based on computational analysis, we observed that miR-139-3p can control the expression of mitogen-activated protein kinase 1 (MAPK1) as a target gene, which is essential for the induction of cardiac hypertrophy and cardiomyocyte apoptosis. This study provides first information that the highly expressed miR-139-3p might be closely involved in MAPK1-mediated cardiac hypertrophy and cardiomyocyte apoptotic processes in 2K1C rat.

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