Study on the Relationship between Cardiomyocyte Apoptosis and Left Ventricular Function in Spontaneously Hypertensive Rats

2021 ◽  
Vol 7 (5) ◽  
pp. 3110-3118
Author(s):  
Jie Chen ◽  
Zhenguo Lu ◽  
Xiaoqian Zhou

At present, hypertension is a relatively common cardiovascular disease. It not only affects the normal operation of target organs such as the heart and kidneys, but also causes cardiovascular and cerebrovascular diseases, which can lead to death. The apoptosis of cardiomyocytes is widespread in the cardiovascular system and is closely related to vascular diseases. Therefore, the purpose of this article is to explore the relationship between changes in left ventricular function, myocardial multidimensional strain and interstitial fibrosis in spontaneously hypertensive rats (SHR) during cardiomyocyte apoptosis. Whether the research is consistent in terms of order, as the age of hypertensive rats increases, whether there is a close connection between myocardial cell apoptosis and the structure and function of the left heart. The method in this article is to use the method of experimental comparison to randomly group 60 experimental mice and observe the changes of various indicators of rats of different ages, from 12 weeks to 84 weeks. The observations include left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (FS), LVEDP, LV+dp/dtmax, LV-dp/dtmax. At the same time, using the TUNEL labeling method, the left ventricular myocardial tissue was sliced, and the apoptosis index of subendocardial and subepicardial myocardial cells was calculated. Then 3 groups were randomly selected from the experimental group, and Western blotting was used to quantitatively detect apoptosis-related the expression of the proteins Bcl-2, Bax, and Fas were compared between the groups. After analysis and determination, it can be found that the apoptosis index of cardiomyocytes is positively correlated with LVMI, CVF, and PVCA (r is 0.83, 0.89, 0.72, respectively, p=0.00). Corresponding conclusions are drawn from the comparison of data. As hypertensive rats grow older, the apoptotic index of cardiomyocytes will continue to increase, and when the myocardial hypertrophy is severe to heart failure, the apoptotic index of cardiomyocytes will increase significantly. This shows that the increase in cardiomyocyte apoptosis is closely related to left heart remodeling, the development of myocardial fibrosis and overall cardiac dysfunction.

1994 ◽  
Vol 267 (5) ◽  
pp. H2050-H2057
Author(s):  
M. E. Christe ◽  
A. A. Perretta ◽  
P. Li ◽  
J. M. Capasso ◽  
P. Anversa ◽  
...  

The purpose of this study was to characterize the effect of chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor on left ventricular function in spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg) was administered in the drinking water continuously for 11 wk, beginning at 4 wk of age. Systolic arterial pressure (SAP) was monitored weekly. At the end of the 11-wk period, left ventricular function was quantified using the perfused working heart preparation. Cilazapril exerted a rapid, complete, and persistent antihypertensive effect in the SHR in vivo but had no effect on SAP in the normotensive Sprague-Dawley (S-D) group. Nevertheless, the drug reduced left ventricular weight to the same extent in both strains. Function of untreated SHR hearts was not different from that of the untreated S-D hearts. Cilazapril treatment depressed heart performance (28–35%) in SHR but had no effect in the S-D group. The decline in pump performance in SHR hearts was associated with diminished tension development and velocity of shortening of papillary muscles. These results demonstrate that an ACE inhibitor, administered to young SHR, produces a reduction in left ventricular contractile function, which may be due to a decline in muscle contractility and which cannot be explained exclusively by the reduction in left ventricular mass.


2008 ◽  
Vol 295 (3) ◽  
pp. H1117-H1121 ◽  
Author(s):  
Dinko Susic ◽  
Xiaoyan Zhou ◽  
Edward D. Frohlich ◽  
Howard Lippton ◽  
Martha Knight

Recent reports have demonstrated a potential role of tissue prorenin in the pathogenesis of cardiovascular and renal damage. This study was designed to examine the role of prorenin in the pathogenesis of target organ damage in spontaneously hypertensive rats (SHRs), the best naturally occurring experimental model of essential hypertension. To this end, we studied 20-wk-old male SHRs receiving a normal diet and 8-wk-old male SHRs given food with 8% NaCl. One-half the rats in each group were given prorenin inhibitor (PRAM-1, 0.1 mg·kg−1·day−1) via osmotic minipumps; the other half served as controls. Arterial pressure, left ventricular function, cardiovascular mass indexes, cardiac fibrosis, and renal function were examined at the end of the experiment. Arterial pressure was unaffected by PRAM-1 in rats on either regular or salt-excess diets. In those rats receiving a normal diet, the blockade of prorenin activation consistently reduced left ventricular mass but affected no other variable. Salt-loaded rats given PRAM-1 for 8 wk demonstrated ( 1) reduced serum creatinine level, ( 2) decreased left ventricular mass, ( 3) improved left ventricular function, and ( 4) reduced left ventricular fibrosis. These data demonstrated that the blockade of nonproteolytic activation of prorenin exerted significant cardiovascular and renal benefit in SHRs with cardiovascular damage produced by salt excess and suggested that the activation of cardiovascular or renal prorenin may be a major mechanism that mediates cardiac and renal damage in this form of accelerated hypertension.


1994 ◽  
Vol 58 (2) ◽  
pp. 116-122 ◽  
Author(s):  
HIKARU NISHIMURA ◽  
JIRO KUBOTA ◽  
MAKOTO OKABE ◽  
MASAKUNI UEYAMA ◽  
TAMIKO OKA ◽  
...  

Hypertension ◽  
1997 ◽  
Vol 30 (5) ◽  
pp. 1029-1034 ◽  
Author(s):  
Javier Díez ◽  
Angel Panizo ◽  
Marta Hernández ◽  
Francisco Vega ◽  
Iosu Sola ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
SureshVarma Penumathsa ◽  
Srikanth Koneru ◽  
Mahesh Thirunavukkarasu ◽  
Lijun Zhan ◽  
Nilanjana Maulik

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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