Development of different phenotypes of hypertensive heart failure

Doi, Ryohei; Masuyama, Tohru; Yamamoto, Keiji; Doi, Yasuji; Mano, Toshiaki; Sakata, Yasushi; Ono, Keiko; Kuzuya, Tsunehiko; Hirota, Seiichi; Koyama, Toru; Miwa, Takeshi; Hori, Masatsugu

doi:10.1097/00004872-200018010-00016

Cited by 157 publications

(34 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1D). At 18 weeks, E/A ratio in HS rats approached values in NS rats (1.46±0.17 vs. 1.60±0.08, p=0.27) consistent with pseudo-normalization of E/A ratio as seen in the progression of diastolic dysfunction 22, 41 (Fig. 1D).…”

Section: Resultssupporting

confidence: 74%

“…1A. In brief, male 7 week-old DSS rats (Charles River Laboratories, MA) underwent baseline transthoracic echocardiography and were then randomly assigned to a high-salt (HS) diet (AIN-76A + 8% NaCl with irradiation, Research Diets, NJ) to induce HFpEF (n=38), 21, 22 or to a normal-salt (NS) diet (AIN-76A [0.3 % NaCl] with irradiation) as controls (n=13). Feeding was continued ad libitum until rats reached the experimental endpoints at 14–18 weeks old.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction

Cho¹,

Zhang²,

Kilfoil³

et al. 2017

Circulation

View full text Add to dashboard Cite

Background Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Methods Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation (PES). QTc interval was measured by surface electrocardiography (ECG). The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and western blotting to investigate changes in ion channel expression. Results After 7 weeks of high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure, hence diagnosed with HFpEF. PES demonstrated increased susceptibility to VA in HFpEF rats (p < 0.001 vs. controls). The arrhythmogenicity index was increased (p < 0.001), and the QTc interval on ECG was prolonged (p < 0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials (p < 0.05) and multiple re-entry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization (p=0.001) and revealed down-regulation of transient outward potassium current (Ito) (p < 0.05). The rapid component of the delayed rectifier potassium current (IKr), and the inward rectifier potassium current (IK1), were also down-regulated (p < 0.05), but the current densities were much lower than for Ito. In accordance with the reduction of Ito, both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Conclusions Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QTc prolongation, delayed repolarization from down-regulation of potassium currents, and multiple re-entry circuits during VA. Our findings are consistent with the hypothesis that potassium current down-regulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction

Cho¹,

Zhang²,

Kilfoil³

et al. 2017

Circulation

View full text Add to dashboard Cite

show abstract

“…Additional possible mechanistic explanations for the dietary-induced changes in cardiac AT 1 R and MR include changes in cardiac filling or BP. Though we did not assess the effect of dietary sodium on cardiac filling in our study, other investigators (Doi et al 2000) have demonstrated that a very high 3 . 2% sodium (8% NaCl) diet for 6 weeks did not alter left ventricular diastolic filling compared to rodents on a low 0 .…”

Section: Discussionmentioning

confidence: 79%

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

Ricchiuti¹,

Lapointe²,

Pojoga³

et al. 2011

Journal of Endocrinology

View full text Add to dashboard Cite

Liberal or high-sodium (HS) intake, in conjunction with an activated renin-angiotensin-aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT 1 R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1 . 6% Na C ) and low-sodium (LS; 0 . 02% Na C ) rat chow was fed to male healthy Wistar rats (nZ7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT 1 R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT 1 R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT 1 R-CAV-3 and MR-CAV-3 complexes, but increased immunoprecipitation of AT 1 R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.

show abstract

“…The DSS model has been reproducibly used to investigate cardiac hypertrophy, diastolic dysfunction, and transition to heart failure (9,16). Therapies shown to attenuate cardiac dysfunction in this model (17,18) ameliorate comparable cardiac abnormalities in humans (19).…”

Section: Discussionmentioning

confidence: 99%

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Bodyak

Ayus²,

Achinger³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

304

250

View full text Add to dashboard Cite

Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH)2D2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS؉PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS؉PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.cardiac hypertrophy ͉ heart failure ͉ paricalcitol ͉ renal failure T he rate of cardiovascular-related mortality in hemodialysis patients is 10-20 times higher than that observed in the general population (1). Left ventricular hypertrophy (LVH) and diastolic dysfunction are present in Ͼ50% of patients at dialysis initiation, and these abnormalities are strongly linked with dialysis-related mortality (2). Currently, there are no well accepted means to modify cardiac structural and functional alterations in renal-failure patients.We recently demonstrated in observational studies that therapy with activated vitamin D to chronic hemodialysis patients is associated with reduction in cardiovascular-related mortality (3, 4). Conversion of nutritional vitamin D (25(OH)D 3 ) to the hormonally active form of vitamin D (1,25(OH) 2 D 3 ) occurs primarily in the kidney; thus, patients with kidney failure commonly present with altered vitamin D status (5). There is growing evidence that vitamin D either directly or indirectly affects cardiac structure and function. The vitamin D receptor knockout mouse model demonstrates increased cardiac renin expression and marked cardiomyocyte hypertrophy (6), and 1,25(OH) 2 D 3 attenuates cardiomyocyte proliferation (7) and hypertrophy (8) in vitro. Here, we demonstrate that treatment with an activated vitamin D compound attenuates the development of cardiac hypertrophy and dysfunction in a recognized animal model of such abnormalities and that comparable findings are evident in humans.

show abstract

Development of different phenotypes of hypertensive heart failure

Cited by 157 publications

References 34 publications

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Contact Info

Product

Resources

About