scholarly journals Atorvastatin Attenuates Myocardial Hypertrophy in Spontaneously Hypertensive Rats via the C/EBPβ/PGC-1α/UCP3 Pathway

2018 ◽  
Vol 46 (3) ◽  
pp. 1009-1018 ◽  
Author(s):  
Yintao Chen ◽  
Ye Chang ◽  
Naijin Zhang ◽  
Xiaofan Guo ◽  
Guozhe Sun ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Myocardial Hypertrophy ◽  
Intervention Group ◽  
Left Ventricular ◽  
Pleiotropic Effects ◽  
Distilled Water ◽  
Hypertensive Rats ◽  
Atorvastatin Treatment ◽  
Spontaneously Hypertensive ◽  
Significant Difference

Background/Aims: Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy. Methods: The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPβ, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis. Results: At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn’t statistically significant difference between the SHR and intervention groups. Staining with Masson’s trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPβ expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks. Conclusion: This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPβ/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy.

Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats

2004 ◽  
Vol 106 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Leila M. M. PEREIRA ◽  
Daniele G. BEZERRA ◽  
Denise L. MACHADO ◽  
Carlos A. MANDARIM-DE-LACERDA
Keyword(s):  
Nitric Oxide ◽  
Body Mass ◽  
Structural Damage ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Genetic Hypertension ◽  
Lv Mass ◽  
Significant Difference

Stereological structural alterations of the heart and kidney were studied in four groups (n=5) of spontaneously hypertensive rats (SHRs) treated for 30 days: (i) control, (ii) NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthesis inhibitor] alone, (iii) enalapril alone and (iv) L-NAME plus enalapril. Blood pressure (BP) was elevated significantly in NO-deficient SHRs (rats receiving L-NAME) or significantly lower in enalapril-treated SHRs. Co-administration of L-NAME and enalapril caused a 20% decrease in BP compared with untreated SHRs. NO-deficient SHRs had a decrease in body mass, but this loss of body mass was prevented efficiently in the enalapril-treated group. Enalapril treatment decreased the left ventricular (LV) mass index in SHRs, even in animals with NO synthesis blocked. NO deficiency in SHRs caused a larger decrease in the number of LV cardiomyocyte nuclei, which had a negative correlation with both LV mass index and BP. The volume-weighted glomerular volume (VWGV) separated the SHRs into two groupings: (i) control and NO-deficient SHRs, and (ii) enalapril- and L-NAME plus enalapril-treated SHRs. There was a significant difference between these two groupings, with VWGV being more than 15% smaller in the latter compared with the former grouping. The present findings reinforce the evidence that enalapril efficiently treats genetic hypertension, and demonstrate that this effect is observed even when NO synthesis is inhibited. Enalapril administration also decreases cardiac and renal structural damage caused by genetic hypertension, as well as by the interaction between genetic hypertension and NO deficiency.

Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats

2005 ◽  
Vol 108 (4) ◽  
pp. 349-355 ◽  
Author(s):  
Daniele G. BEZERRA ◽  
Carlos A. MANDARIM-de-LACERDA
Keyword(s):  
Left Ventricle ◽  
Spontaneously Hypertensive Rats ◽  
Renal Cortex ◽  
Interstitial Fibrosis ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Significant Difference

The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss.

scholarly journals Vasorelaxation effect of Syzygium polyanthum (wight) walp. Leaves extract on isolated thoracic aorta rings of normal and hypertensive rats

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Azlini Ismail ◽  
Wan Amir Nizam Wan Ahmad
Keyword(s):  
Thoracic Aorta ◽  
Spontaneously Hypertensive Rats ◽  
Negative Control ◽  
Distilled Water ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Traditional Remedy ◽  
Ic50 Value ◽  
Significant Difference ◽  
Wistar Kyoto

Introduction: Syzygium polyanthum (Wight) Walp. leaves are traditionally consumed by the Malays as an alternative treatment for hypertension. Until now, effect of S. polyanthum leaves extract on blood vessel is not yet disclosed. Methods: This study investigated the effect of S. polyanthum leaves aqueous extract (AESP) (0.01, 0.1, 1 & 10 mg/ml) on isolated thoracic aorta rings of normotensive Wistar-Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR). Both rings were pre-contracted using phenylephrine (1 µM). Distilled water that dissolved AESP served as negative control. Results: As compared to negative control, AESP at 0.1, 1, and 10 mg/ml significantly relaxed aorta rings of WKY by 39.81 ± 2.99 % (P<0.001), 59.55 ± 7.60 % (P<0.001), and 72.58 ± 5.57 % (P<0.001), respectively. In SHR, AESP at 1 and 10 mg/ml significantly relaxed the aorta rings of SHR by 40.53 ± 3.66 % (P<0.001) and 65.73 ± 8.24 % (P<0.001), respectively. There was a significant difference between AESP-induced vasorelaxation in WKY and in SHR at a concentration of 0.1 mg/ml (P<0.001). The IC50 value for AESPinduced vasorelaxation on aorta rings of WKY (94.67 ± 1.41 µg/ml) was lower than of SHR (799.80 ± 1.69 µg/ml). Conclusions: The S. polyanthum leaves extract was able to cause significant relaxation on aorta rings of both normal and hypertensive rats. Thus, this finding is well-corroborated with the use of this plant as a traditional remedy for hypertension. It is suggested that an in-depth investigation of  the mechanism of vasorelaxation of this plant is carried-out in the future.

scholarly journals The HuoXue DiTan Recipe Attenuates Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats by Increasing Autophagy Through the PTEN/PI3K/AKT/mTOR Pathway

2021 ◽  
Author(s):  
YAO Jiamei ◽  
ZHANG Cui ◽  
YANG Yushu ◽  
YANG Haiyan ◽  
ZHANG Dan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Left Ventricular Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Ventricular Hypertrophy ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Mtor Pathway ◽  
Mtor Signaling Pathway ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) is associated with a reduction in autophagy, which can be inhibited by disruption of the PTEN/PI3K/AKT/mTOR pathway. The HuoXue DiTan recipe (HDR) is a commonly used prescription that has shown therapeutic effects on hypertension and its complications. However, its mechanisms are still unclear. In the present study, we hypothesized that HDR can regulate the PTEN/PI3K/AKT/mTOR signaling pathway and thereby reverse LVH by increasing autophagy in spontaneously hypertensive rats. Methods Twelve-week-old male spontaneously hypertensive (SH) rats and age-matched normotensive-control Wistar-Kyoto (WKY) rats were divided into four groups. After 12 weeks of treatment, echocardiographic measurements were made on the left ventricle, blood samples were collected for oxidative stress analysis, left ventricle tissue was processed for hematoxylin and eosin, Masson's trichrome, and immunohistochemical/ immunofluorescence staining, and TUNEL, RT-qPCR and Western blot analyses were performed. Results Compared with age-matched WKY rats, SH rats at 16 weeks of age exhibited significantly greater myocardial hypertrophy and remodeling with abnormal heart function. There was a reduction in autophagy and increase in apoptosis, resulting in an imbalance of oxidative stress manifested as left ventricular hypertrophy and impaired cardiac function. These effects may be related to a decrease in PTEN expression, which leads to activation of the PI3K/AKT/mTOR signaling pathway, resulting in abnormal expression of autophagy- and apoptosis-related proteins. After 12 weeks of HDR administration, blood pressure and ventricular hypertrophy were reduced, MDA and SOD levels and NADPH oxidase activity were better regulated, and gene expression of myocardial hypertrophy markers (ANP and β-MHC) was inhibited. HDR can promote autophagy and inhibit apoptosis, which may be related to regulation of autophagy- and apoptosis-related genes and proteins. HDR can also induce autophagy by enhancing expression of PTEN and inhibiting activation of the PI3K/AKT/mTOR signal pathway. Importantly, we demonstrated that VO-Ohpic, an inhibitor of PTEN, could suppress the effect of HDR on LVH in spontaneously hypertensive rats. Conclusion In conclusion, these results provide evidence for an important role of HDR in inhibition of left ventricular hypertrophy in spontaneously hypertensive rats, and indicate that it may act by improving autophagy through the PTEN/PI3K/AKT /mTOR pathway.

scholarly journals High-calorie diet influence on morphological and functional parameters of the cardiovascular system in spontaneously hypertensive rats

2021 ◽  
Vol 10 (1) ◽  
pp. 50-57
Author(s):  
A.Yu. Ivanova ◽  
◽  
E.Yu. Rysenkova ◽  
M.A. Afanasiev ◽  
P.V. Chumachenko ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Spontaneously Hypertensive Rats ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Control Group ◽  
Chow Diet ◽  
Standard Diet ◽  
High Fat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Introduction. Hypertension with left ventricular hypertrophy (LVH) is a major independent risk factor for cardiovascular-related morbidity. Diet plays an essential role in the prevention and treatment of chronic cardiovascular disease. The aim of our study was to analyze the influence of 10-week diets consisting of different high fats and carbohydrates on the myocardium in spontaneously hypertensive rats (SHR). Materials and methods. The SHR (n=34) and WKY (n=34) were randomly divided into five groups (n=6 or 7 per group). For 10 weeks, the control group was fed the standard diet; the experimental groups were fed the standard chow diet with the different fats and sucrose (11% of the calorie intake). Systolic blood pressure (SBP) was measured before the experiment and 10 weeks after by the non-invasive tail-cuff method. After the experiment, the animals were humanely sacrificed. The heart specimens after routine processing were stained with hematoxylin and eosin. We determined the thickness of the left ventricle and the number of cardiomyocyte nuclei per unit area using morphometry. Results. An increase in SBP at the end of the experiment was found in SHR animals in groups receiving trans-fat and sucrose by 10.9 mm Hg and 13.4 mm Hg, respectively. Myocardial hypertrophy was observed in the SHR Butter group. Conclusion. We found that the increased content of trans-fats and sucrose in the diet leads to an increase in SBP in spontaneously hypertensive rats; saturated fatty acids – to myocardial hypertrophy in spontaneously hypertensive rats without aggravation of systolic hypertension. In normotensive animals, no negative effect of the high-fat diet on the cardiovascular system was observed. Keywords: myocardial hypertrophy, arterial hypertension, high fat diets, palm oil, carbohydrates

scholarly journals Progressive Myocardial Apoptosis and Cardiac Dysfunction in Spontaneously Hypertensive Rats During Aging

2020 ◽  
Vol 33 (2) ◽  
pp. 205-205
Author(s):  
Yun Wu ◽  
Li-yun Fu ◽  
Qin-yun Ruan ◽  
Lei Yan ◽  
Chun-yan Huang ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Myocardial Apoptosis ◽  
Significant Difference ◽  
Related Proteins

Abstract Objective To investigate myocardial apoptosis and the expression of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bax], cardiac hypertrophy, and function in spontaneously hypertensive rats (SHR) during aging. Methods Male SHR (n = 36) and Wistar-Kyoto rats (WKY, n = 30) were monitored for their cardiac function from 14 to 102 weeks of age using echocardiography. Myocardial apoptosis in the subendocardium and subepicardium was analyzed using TUNEL staining. The apoptosis-related proteins (Bcl-2 and Bax) were assessed by Western blot analysis. Results Left ventricular mass index (LVMI) in SHR increased progressively with age. Left ventricular ejection fraction (LVEF) showed no significant difference from 14 to 66 weeks of age, but decreased significantly in SHR from 84 to 102 weeks of age. The apoptotic index (APOI) of myocardial cells in SHR increased with age, in which subendocardial APOI (APOI-endo) increased at 66 weeks and was significantly higher than the age-matched WKY (9.83 ± 3.97 vs. 4.03 ± 2.06, P &lt; 0.05). Additionally, the subepicardial APOI (APOI-epi) increased significantly at 84 weeks of age (P &lt; 0.05). Bax/Bcl-2 ratio was higher in SHR than WKY at 66 weeks (3.98 ± 0.80 vs. 0.29 ± 0.06, P &lt; 0.05), and enhanced further at 102 weeks of age (10.54 ± 1.60 vs. 0.70 ± 0.13, P &lt; 0.05). Myocardial APOI was positively correlated with LVMI (r = 0.83, P &lt; 0.01), negatively with LVEF in 66–102 weeks (r = −0.81, P &lt; 0.01), and positively with Bax/Bcl-2 ratio (r = 0.79, P &lt; 0.01). Conclusion Myocardial apoptosis increases with aging and is associated with progressive left ventricular remodeling and cardiac dysfunction in SHR.

Abstract 408: Thioredoxin-1 Gene Delivery Induces Hemeoxygenase-1 Mediated Myocardial Preservation after Chronic Infarction in Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
SureshVarma Penumathsa ◽  
Srikanth Koneru ◽  
Mahesh Thirunavukkarasu ◽  
Lijun Zhan ◽  
Nilanjana Maulik
Keyword(s):  
Left Ventricle ◽  
Western Blot ◽  
Infarct Size ◽  
Blot Analysis ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Thioredoxin 1 ◽  
Lac Z

Hypertension the major risk factor for many cardiovascular diseases is a result of multiple causes along with excessive generation of reactive oxygen species resulting in imbalance of redox status. Thioredoxin-1 (Trx-1) is a redox regulatory multifunctional protein with anti-inflammatory, anti-apoptotic and antioxidant effects. In the present study we investigated the therapeutic potential of Adeno-Trx-1 in spontaneously hypertensive rats (SHR). The rats were assigned to four different groups (n = 24) such as (1) normotensive Wistar Kyoto (WKY) (2) SHR (3) SHR +Adeno-Lac-Z (SHRLac-Z) and (4) SHR +Adeno-Trx-1 (SHRTrx-1). Echo-guided gene delivery to the anterior wall of left ventricle was performed using 1x109 pfu of adenovirus constructed with Trx-1 and Lac-Z. Two days after injection of adeno virus, the hearts were subjected to permanent left anterior descending coronary artery occlusion (MI). Left ventricular functions by Echocardiography were examined after 30 days of MI as the significant changes in left ventricle were observed after 4 weeks of MI. Decreased left ventricular inner diameter (7 vs 9 mm) and increased ejection fraction (52 vs 42 %), fractional shortening (28 vs 22 %) was observed in SHRTrx-1 compared to SHR. Infarct size, cardiomyocyte apoptosis and protein expression profiles (by Confocal and Western blot analysis) were observed at predetermined time points i.e after 24 and 48 hours of MI respectively. Decreased infarct size (52% vs 67%), cardiomyocyte apoptosis by TUNEL assay (161 vs 240) and increased expression of Trx-1 and HO-1 were observed in SHRTrx-1 compared to SHR. Confocal results were also confirmed by Western blot analysis. Results documented increased expression of Trx-1 (1.8 fold) and HO-1 (1.4 fold) in SHRTrx-1 as compared to SHR. In addition, we have also observed increased expression of anti-apoptotic protein Bcl-2 (1.7 fold) in SHRTrx-1 treated group compared SHR. Thus our results demonstrate for the first time that the cardioprotective effect of Adeno-Trx-1 therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent a novel mechanism for therapy against hypertension induced post infarction heart failure.

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