A study of prevention and regression of cardiac hypertrophy with a prolactin inhibitor in a biological model of ventricular hypertrophy caused by aorto caval fistulae in rat

1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P<0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.

Download Full-text

Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat

European Heart Journal ◽

10.1093/eurheartj/4.suppl_a.143 ◽

1983 ◽

Vol 4 (suppl A) ◽

pp. 143-148 ◽

Cited By ~ 20

Author(s):

J. M. Pfeffer ◽

M. A. Pfeffer ◽

I. Mirsky ◽

E. Braunwald

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Spontaneously Hypertensive Rat ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Regression Of Cardiac Hypertrophy

Download Full-text

Calcineurin Inhibitor Attenuates the Development and Induces the Regression of Cardiac Hypertrophy in Rats With Salt-Sensitive Hypertension

Circulation ◽

10.1161/01.cir.102.16.1996 ◽

2000 ◽

Vol 102 (16) ◽

pp. 1996-2004 ◽

Cited By ~ 27

Author(s):

Masaki Shimoyama ◽

Doubun Hayashi ◽

Yunzeng Zou ◽

Eiki Takimoto ◽

Miho Mizukami ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Calcineurin Inhibitor ◽

Regression Of Cardiac Hypertrophy ◽

Salt Sensitive Hypertension

Download Full-text

Regression of Cardiac Hypertrophy Following Experimental Hyperthyroidism in Rats

Experimental Biology and Medicine ◽

10.3181/00379727-136-35331 ◽

1971 ◽

Vol 136 (2) ◽

pp. 645-648 ◽

Cited By ~ 11

Author(s):

E. J. Van Liere ◽

D. A. Sizemore

Keyword(s):

Cardiac Hypertrophy ◽

Experimental Hyperthyroidism ◽

Regression Of Cardiac Hypertrophy

Download Full-text

The SRSF4-GAS5-Glucocorticoid Receptor Axis Regulates Ventricular Hypertrophy

Circulation Research ◽

10.1161/circresaha.120.318577 ◽

2021 ◽

Author(s):

Javier Larrasa-Alonso ◽

María Villalba ◽

Carlos Martí-Gómez ◽

Paula Ortiz-Sánchez ◽

Marina López-Olañeta ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Cardiac Hypertrophy ◽

Diastolic Dysfunction ◽

Ventricular Hypertrophy ◽

Transcriptional Activity ◽

Rna Binding ◽

Rna Binding Proteins ◽

Left Ventricular ◽

Therapeutic Tools ◽

Nucleotide Resolution

Rationale: RNA-binding proteins (RBPs) play critical roles in human biology and disease. Aberrant RBP expression affects various steps in RNA processing, altering the function of the target RNAs. The RBP serine/arginine-rich splicing factor 4 (SRSF4) has been linked to neuropathies and cancer. However, its role in the heart is completely unknown. Objective: To investigate the role of SRSF4 in the heart. Methods and Results: Echocardiography of mice specifically lacking SRSF4 in the heart (SRSF4 KO) revealed left ventricular hypertrophy and increased cardiomyocyte area, which led to progressive diastolic dysfunction with age. SRSF4 KO mice showed altered electrophysiological activity under isoproterenol-induced cardiac stress, with a post-QRS depression and a longer QT interval, indicating an elevated risk of sudden cardiac death. RNA-Seq analysis revealed expression changes in several long non-coding RNAs (lncRNAs), including GAS5 (growth arrest specific 5), which we identified as a direct SRSF4 target in cardiomyocytes by individual-nucleotide-resolution cross-linking and immuno-precipitation (iCLIP). GAS5 is a repressor of the glucocorticoid receptor (GR) and was downregulated in SRSF4 KO hearts. This corresponded with elevated GR transcriptional activity in cardiomyocytes, leading to increases in hypertrophy markers and cell size. Furthermore, hypertrophy in SRSF4 KO cardiomyocytes was reduced by overexpressing GAS5. Conclusions: Loss of SRSF4 expression results in cardiac hypertrophy, diastolic dysfunction, and abnormal repolarization. The molecular mechanism underlying this effect involves GAS5 downregulation and consequent elevation of GR transcriptional activity. Our findings may help to develop new therapeutic tools for the treatment of cardiac hypertrophy and myocardial pathology in Cushing's syndrome patients.

Download Full-text

Regression of Cardiac Hypertrophy with Antihypertensive Therapy

InPharma ◽

10.1007/bf03308839 ◽

1988 ◽

Vol 652 (1) ◽

pp. 15-15

Keyword(s):

Cardiac Hypertrophy ◽

Antihypertensive Therapy ◽

Regression Of Cardiac Hypertrophy

Download Full-text

Coordinated changes in contractility, energetics, and isomyosins after aortic stenosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.252.2.h275 ◽

1987 ◽

Vol 252 (2) ◽

pp. H275-H282

Author(s):

Y. Lecarpentier ◽

L. B. Bugaisky ◽

D. Chemla ◽

J. J. Mercadier ◽

K. Schwartz ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Peak Power ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Ascending Aorta ◽

Peak Power Output ◽

Shortening Velocity ◽

Old Rats ◽

Quantitative Changes

To investigate possible alterations of myocardial performance in young rats, cardiac hypertrophy was induced by stenosis of the ascending aorta (AS) in three groups of 25-day-old rats that were compared with three groups of sham-operated controls (C). The cardiac overload duration was 8-10 days, 1 mo, and 2 mo in groups 1, 2, and 3, respectively. Mechanics and energetics were studied in left ventricular papillary muscles, and determination of the V1 and V3 isomyosin pattern was achieved in the same papillary muscle. The majority of quantitative changes concerning the cardiac growth process, contractility, and isomyosin shifts occurred within 8-10 days of stenosis. At this point, the degree of left ventricular hypertrophy relative to C was 53 +/- 6%, whereas maximum unloaded shortening velocity (Vmax) decreased significantly (2.8 +/- 0.1 in C vs. 1.9 +/- 0.1 Lmax/s in AS), peak power output (Emax) decreased (1.8 +/- 0.3 in C vs. 0.6 +/- 0.1 in AS), and the curvature of Hill's hyperbola increased (1.3 +/- 0.4 in C vs. 2.0 +/- 0.7 in AS); moreover, the percent V1 isomyosin decreased significantly (98 +/- 1 in C vs. 51 +/- 3% in AS) and the percent V3 isomyosin increased significantly (2 +/- 1 in C vs. 26 +/- 2% in AS). Beyond 8-10 days of AS, additional changes in cardiac hypertrophy and in mechanical and biochemical parameters were less marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text