Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker

2007 ◽  
Vol 292 (2) ◽  
pp. R946-R954 ◽  
Author(s):  
Tomohito Ohtani ◽  
Miho Ohta ◽  
Kazuhiro Yamamoto ◽  
Toshiaki Mano ◽  
Yasushi Sakata ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mineralocorticoid Receptor ◽  
Cardiac Tissue ◽  
Diastolic Heart Failure ◽  
Tissue Level ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Beneficial Effects ◽  
Aldosterone Production ◽  
Ventricular Fibrosis

Cardiac aldosterone levels have not been evaluated in diastolic heart failure (DHF), and its roles in this type of heart failure remain unclear. This study aimed to detect cardiac aldosterone by use of a liquid chromatographic-mass spectrometric method and to assess the effects of mineralocorticoid receptor blockade on hypertensive DHF. Dahl salt-sensitive rats fed 8% NaCl diet from 7 wk (hypertensive DHF model) were divided at 13 wk into three groups: those treated with subdepressor doses of eplerenone (12.5 or 40 mg·kg−1·day−1) and an untreated group. Dahl salt-sensitive rats fed 0.3% NaCl diet served as controls. Cardiac aldosterone was detected in the DHF rats but not in the control rats, with increased ventricular levels of mineralocorticoid receptor. Cardiac levels of 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone were not different between the control and DHF rats, but the tissue level of corticosterone that has an affinity to mineralocorticoid receptor was 1,000 times as high as that of aldosterone. Aldosterone synthase activity and CYP11B2 mRNA were undetectable in the ventricular tissue of the DHF rats. Administration of eplerenone attenuated ventricular hypertrophy, ventricular fibrosis, myocardial stiffening, and relaxation abnormality, leading to the prevention of overt DHF. In summary, the myocardial aldosterone level increased in the DHF rats. However, its value was extremely low compared with corticosterone, and no evidence for enhancement of intrinsic myocardial aldosterone production was found. The upregulation of mineralocorticoid receptor may play a central role in the pathogenesis of DHF, and blockade of mineralocorticoid receptor is likely an effective therapeutic regimen of DHF.

Preventive for onset of diastolic heart failure in hypertension -beneficial effects of angiotensin II type 1 receptor antagonist

1998 ◽  
Vol 4 (3) ◽  
pp. 68
Author(s):  
Reiko Doi ◽  
Tohru Masuyama ◽  
Kazuhiro Yamamoto ◽  
Keiko Ono ◽  
Hiroya Kondo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Diastolic Heart Failure ◽  
Beneficial Effects

scholarly journals Neuregulins: protective and reparative growth factors in multiple forms of cardiovascular disease

2020 ◽  
Vol 134 (19) ◽  
pp. 2623-2643
Author(s):  
Andrew Geissler ◽  
Sergey Ryzhov ◽  
Douglas B. Sawyer
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Tyrosine Kinases ◽  
Cardiac Myocyte ◽  
Diastolic Heart Failure ◽  
Systolic Heart Failure ◽  
Circulatory System ◽  
Cardiovascular Responses ◽  
Adaptive Responses ◽  
Beneficial Effects

Abstract Neuregulins (NRGs) are protein ligands that act through ErbB receptor tyrosine kinases to regulate tissue morphogenesis, plasticity, and adaptive responses to physiologic needs in multiple tissues, including the heart and circulatory system. The role of NRG/ErbB signaling in cardiovascular biology, and how it responds to physiologic and pathologic stresses is a rapidly evolving field. While initial concepts focused on the role that NRG may play in regulating cardiac myocyte responses, including cell survival, growth, adaptation to stress, and proliferation, emerging data support a broader role for NRGs in the regulation of metabolism, inflammation, and fibrosis in response to injury. The constellation of effects modulated by NRGs may account for the findings that two distinct forms of recombinant NRG-1 have beneficial effects on cardiac function in humans with systolic heart failure. NRG-4 has recently emerged as an adipokine with similar potential to regulate cardiovascular responses to inflammation and injury. Beyond systolic heart failure, NRGs appear to have beneficial effects in diastolic heart failure, prevention of atherosclerosis, preventing adverse effects on diabetes on the heart and vasculature, including atherosclerosis, as well as the cardiac dysfunction associated with sepsis. Collectively, this literature supports the further examination of how this developmentally critical signaling system functions and how it might be leveraged to treat cardiovascular disease.

Prospects for the use of thyroid hormones in patients with heart failure

2021 ◽  
Author(s):  
S. M. Pyvоvar ◽  
Yu. S. Rudyk ◽  
О. B. Krоtоva ◽  
L. V. Panina
Keyword(s):  
Heart Failure ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Animal Studies ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Heart Function ◽  
Experimental Studies ◽  
Tissue Level ◽  
Free Triiodothyronine

Thyroid hormone therapy in the setting of heart failure is still an «open book» today. There are several unanswered questions: the regimen, doses and schedule of the use of thyroid hormones, the consequences of such therapy. At the same time, the presence of a comorbid pathology of the thyroid gland, which requires the appointment of levothyroxine, allows one to partially answer these questions. Thyroid hormones affect the diastolic and systolic functions of the myocardium. Ventricular contractile function is also affected by changes in hemodynamic conditions secondary to thyroid hormones and peripheral vascular tone. Thyroid hormone homeostasis maintains a positive ventricular-arterial ratio, resulting in a favorable balance for heart function. Experimental studies in rats have shown that chronic hypothyroidism alone can eventually lead to heart failure. Other studies suggest a decrease in the level of free triiodothyronine in the myocardium after myocardial infarction or with arterial hypertension due to the activation of type 3 deiodinase, which leads to deactivation of triiodothyronine and thyroxine. To address these issues, the researchers propose conducting multicenter, randomized, placebo-controlled trials to evaluate the effects of thyroxine replacement in patients with chronic heart failure. The review highlights the growing body of evidence from animal studies and small clinical trials that suggests that low thyroid activity at the cardiac tissue level can negatively affect the progression of heart failure and that treatment with thyroid hormones can lead to an improved prognosis.

Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure

2001 ◽  
Vol 79 (8) ◽  
pp. 730-735 ◽  
Author(s):  
Michihiro Yoshimura ◽  
Hirofumi Yasue ◽  
Hisao Ogawa
Keyword(s):  
Heart Failure ◽  
Cardiac Tissue ◽  
Cardiac Effect ◽  
Sympathetic Nervous Systems ◽  
Patients With Heart Failure ◽  
Key Factor ◽  
Aldosterone Production ◽  
Myocardial Stretch ◽  
Important Position ◽  
Stimulation Of

Plasma levels of ANP and BNP increase in accordance with the severity of the heart failure. In severe cases, the amount of BNP secreted surpasses that of ANP. The main secretion site of BNP is the ventricles, and that of ANP is the atria. However, ANP is also secreted from the ventricles as heart failure advances, and thus the ventricles are important sites for both BNP and ANP. It is well known that myocardial stretch is a key factor in the stimulation of the secretion of ANP and BNP, although neurohumoral factors also play a role in the secretion mechanism. The major physiological effects of ANP and BNP are vasodilation, natriuresis, and inhibition of the renin-angiotensin-aldosterone (RAA) and the sympathetic nervous systems; all of which are supposed to suppress the progression of heart failure. The inhibitory action of ANP and BNP on the RAA system has been considered to be an extra-cardiac effect. We recently reported the activation of an angiotensin-converting enzyme and aldosterone production in failing human hearts. ANP and BNP, however, would inhibit aldosterone production, not only in the adrenal cortex but also in cardiac tissue. ANP, and especially BNP, are useful markers of the heart's status during treatment for heart failure. The infusion of synthetic ANP (hANP) or BNP (Nesiritide®) is effective in the treatment of acute heart failure. In Japan, BNP occupies an important position in the diagnosis of chronic heart failure, as ANP does in the treatment of acute heart failure.Key words: natriuretic peptide, heart failure, myocardial infarction, cardiomyopathy, aldosterone.

scholarly journals Spironolactone in cardiovascular disease: an expanding universe?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1738 ◽  
Author(s):  
John W. Funder
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Diastolic Heart Failure ◽  
Secondary Hypertension ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonist ◽  
Reduced Ejection Fraction ◽  
The Third ◽  
Renal Artery Denervation

Spironolactone has been marketed for over half a century as a ‘potassium-sparing diuretic’, used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i.e. with a preserved ejection fraction). The third currently accepted role for spironolactone is in hypertension resistant to three conventional antihypertensives including a diuretic, where it has been proven to be effective, in contra-distinction to renal artery denervation. Finally, brief consideration will be given to ‘areas in waiting’ – pulmonary hypertension/fibrosis, cancer – where spironolactone may play very useful roles.

Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure

2015 ◽  
Vol 309 (10) ◽  
pp. H1629-H1641 ◽  
Author(s):  
Rodrigo W. A. Souza ◽  
Geysson J. Fernandez ◽  
João P. Q. Cunha ◽  
Warlen P. Piedade ◽  
Luana C. Soares ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Regulatory Networks ◽  
Target Genes ◽  
Cardiac Tissue ◽  
Aerobic Exercise Training ◽  
Cytokine Signaling ◽  
Protective Mechanisms ◽  
Beneficial Effects ◽  
Systolic And Diastolic Function

Exercise training (ET) has beneficial effects on the myocardium in heart failure (HF) patients and in animal models of induced cardiac hypertrophy and failure. We hypothesized that if microRNAs (miRNAs) respond to changes following cardiac stress, then myocardial profiling of these miRNAs may reveal cardio-protective mechanisms of aerobic ET in HF. We used ascending aortic stenosis (AS) inducing HF in Wistar rats. Controls were sham-operated animals. At 18 wk after surgery, rats with cardiac dysfunction were randomized to 10 wk of aerobic ET (HF-ET) or to a heart failure sedentary group (HF-S). ET attenuated cardiac remodeling as well as clinical and pathological signs of HF with maintenance of systolic and diastolic function when compared with that of the HF-S. Global miRNA expression profiling of the cardiac tissue revealed 53 miRNAs exclusively dysregulated in animals in the HF-ET, but only 11 miRNAs were exclusively dysregulated in the HF-S. Out of 23 miRNAs that were differentially regulated in both groups, 17 miRNAs exhibited particularly high increases in expression, including miR-598, miR-429, miR-224, miR-425, and miR-221. From the initial set of deregulated miRNAs, 14 miRNAs with validated targets expressed in cardiac tissue that respond robustly to ET in HF were used to construct miRNA-mRNA regulatory networks that revealed a set of 203 miRNA-target genes involved in programmed cell death, TGF-β signaling, cellular metabolic processes, cytokine signaling, and cell morphogenesis. Our findings reveal that ET attenuates cardiac abnormalities during HF by regulating cardiac miRNAs with a potential role in cardio-protective mechanisms through multiple effects on gene expression.

scholarly journals Beneficial effects of bisoprolol on the survival of hypertensive diastolic heart failure model rats

2008 ◽  
Vol 10 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Mayu Nishio ◽  
Yasushi Sakata ◽  
Toshiaki Mano ◽  
Tomohito Ohtani ◽  
Yasuharu Takeda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Heart Failure ◽  
Failure Model ◽  
Beneficial Effects ◽  
Heart Failure Model

ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure

2005 ◽  
Vol 23 (2) ◽  
pp. 393-400 ◽  
Author(s):  
Kazuhiro Yamamoto ◽  
Toshiaki Mano ◽  
Junichi Yoshida ◽  
Yasushi Sakata ◽  
Nagahiro Nishikawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Ace Inhibitor ◽  
Diastolic Heart Failure ◽  
Receptor Blocker ◽  
Ventricular Fibrosis

Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure

2007 ◽  
Vol 29 (3) ◽  
pp. 246-252 ◽  
Author(s):  
Natale P. L. Rolim ◽  
Alessandra Medeiros ◽  
Kaleizu T. Rosa ◽  
Katt C. Mattos ◽  
Maria C. Irigoyen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Cardiac Myocyte ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Exercise Intolerance ◽  
Computer Assisted ◽  
Wild Type ◽  
Beneficial Effects ◽  
Ventricular Fibrosis

The molecular basis of the beneficial effects associated with exercise training (ET) on overall ventricular function (VF) in heart failure (HF) remains unclear. We investigated potential Ca2+ handling abnormalities and whether ET would improve VF of mice lacking α2A- and α2C-adrenoceptors (α2A/α2CARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic α2A/α2CARKO mice in a C57BL/J genetic background (5–7 mo of age) was randomly assigned into untrained and trained groups. VF was assessed by two-dimensional guided M-mode echocardiography. Cardiac myocyte width and ventricular fibrosis were evaluated with a computer-assisted morphometric system. Sarcoplasmic reticulum Ca2+ ATPase (SERCA2), phospholamban (PLN), phospho-Ser16-PLN, phospho-Thr17-PLN, phosphatase 1 (PP1), and Na+-Ca2+ exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. α2A/α2CARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in α2A/α2CARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in α2A/α2CARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser16-PLN (63%), phospho-Thr17-PLN (211%) in α2A/α2CARKO mice. Furthermore, ET restored NCX and PP1 expression in α2A/α2CARKO to untrained WT mice levels. Thus, we provide evidence that Ca2+ handling is impaired in this HF model and that overall VF improved upon ET, which was associated to changes in the net balance of cardiac Ca2+ handling proteins.

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