Cardiac Endothelin-1 Plays a Critical Role in the Functional Deterioration of Left Ventricles During the Transition From Compensatory Hypertrophy to Congestive Heart Failure in Salt-Sensitive Hypertensive Rats

Iwanaga, Yoshitaka; Kihara, Yasuki; Hasegawa, Koji; Inagaki, Kenji; Yoneda, Tomohiro; Kaburagi, Satoshi; Araki, Makoto; Sasayama, Shígetake

doi:10.1161/01.cir.98.19.2065

Cited by 142 publications

(103 citation statements)

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“…Consistent with our previous reports, 12,13 in DS rats at the LVH stage, the LV tissue ET-1 peptide level was within normal limits, contrasting with the abrupt and massive increase at the CHF stage. On the other hand, the tissue AII was already activated in the LVH stage and remained active throughout the study period.…”

Section: Izumi Et Al Et-1 Induces I Cat In Ventricular Myocytes 2533supporting

confidence: 92%

“…10 We report that the reappearance of this type of Ca 2ϩ channel is tightly regulated by the local neurohumoral environment, especially by tissue endothelin (ET)-1 but not by angiotensin II (AII), through the use of cultured adult ventricular myocytes and an animal model in which the transition from compensatory LV hypertrophy to failure was distinctively observed. [11][12][13] Our data suggest that suppression of I Ca,T may be achieved by pharmacological regulation over the tissue neurohumoral condition of the failing myocardium in this animal model.…”

mentioning

confidence: 64%

“…[11][12][13] In DS rats, a state of compensatory concentric left ventricular hypertrophy (LVH, nϭ16) is obtained at the age of 11 weeks, followed by LV dilation, global hypokinesis, and pulmonary congestion (CHF, nϭ22) at the age of 16 to 18 weeks. 11,12 Normotensive DR rats were used as age-matched control animals (11-week-old animals, nϭ16; 17-week-old, nϭ16). Fourteen LVH-DS rats were subjected to chronic treatment with bosentan (100 mg/kg per day PO) 13 …”

Section: Animal Model Of Cardiac Hypertrophy and Failurementioning

confidence: 99%

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Reinduction of T-Type Calcium Channels by Endothelin-1 in Failing Hearts In Vivo and in Adult Rat Ventricular Myocytes In Vitro

et al. 2003

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Background-In ventricular myocardium, the T-type Ca 2ϩ current (I Ca,T ), which is temporarily observed during fetal and neonatal periods, has been shown to reappear in failing/remodeling hearts. However, its pathophysiological regulation has not been elucidated. Methods and Results-We utilized Dahl salt-sensitive (DS) rats with hypertension at the stage of concentric left ventricular (LV) hypertrophy (11 weeks old, LVH) and at the heart failure stage (16 to 18 weeks old, CHF). Some were treated with bosentan (100 mg/kg per day) during the period from LVH to CHF. In LVH, neither the presence of I Ca,T (measured in the freshly isolated LV myocytes) nor an increase in ␣-1G mRNA expression were detected. This condition was associated with increases in tissue angiotensin II (AII) but not with endothelin (ET)-1 peptides. In contrast, in CHF, when the tissue AII remained elevated and ET-1 de novo increased, I Ca,T was recorded in most of the cells (Ϫ0.87Ϯ0.18 pA/pF at Ϫ30 mV, PϽ0.01 versus LVH). This was associated with a significant increase in the ␣-1G mRNA level. The chronic bosentan treatment eliminated both the elevation of ␣-1G mRNA level and I Ca,T from the cells, whereas it did not affect the cell size and membrane capacitance. In addition, 48-hour exposure to ET-1 but not AII induced I Ca,T in normal adult myocytes in culture from Sprague-Dawley rats. Conclusions-I

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Section: Izumi Et Al Et-1 Induces I Cat In Ventricular Myocytes 2533supporting

confidence: 92%

mentioning

confidence: 64%

Section: Animal Model Of Cardiac Hypertrophy and Failurementioning

confidence: 99%

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Reinduction of T-Type Calcium Channels by Endothelin-1 in Failing Hearts In Vivo and in Adult Rat Ventricular Myocytes In Vitro

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“…The Dahl S model of hypertensive disease is characterized by elevated blood pressure and the development of heart failure in response to a HS diet (22,24). SBP measurements in Dahl S animals confirmed an early onset and sustained increase in blood pressure in animals fed a 8% NaCl diet (HS) (supplementary Fig.…”

Section: Resultsmentioning

confidence: 90%

“…Ultimately, the Dahl S genetic rat strain develops a sustained elevation in systolic blood pressure (SBP) that may exceed 200 mmHg when given a HS diet, with evidence of compensatory hypertrophy and congestive heart failure (22,24). A loss of cerebral blood flow autoregulation followed by blood-brain barrier disruption and hypertensive encephalopathy has also been observed in these animals (47).…”

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confidence: 99%

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB

Rose¹,

Bond²,

Tighe³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Rose P, Bond J, Tighe S, Toth MJ, Wellman TL, de Montiano EM, Lewinter MM, Lounsbury KM. Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB. Am J Physiol Heart Circ Physiol 294: H1075-H1085, 2008. First published December 21, 2007 doi:10.1152/ajpheart.00913.2007.-Although changes in gene expression are necessary for arterial remodeling during hypertension, the genes altered and their mechanisms of regulation remain uncertain. The goal of this study was to identify cerebral artery genes altered by hypertension and define signaling pathways important in their regulation. Intact cerebral arteries from Dahl salt-sensitive normotensive and hypertensive high-salt (HS) rats were examined by immunostaining, revealing an increased phosphorylation of extracellular signalregulated kinase 1/2 (ERK1/2) and expression of the proliferative marker Ki-67 in arteries from hypertensive animals. Arterial RNA analyzed by microarray and validated with RT-quantitative PCR revealed that jun family member junB and matricellular genes plasminogen activator inhibitor-1 (PAI-1) and osteopontin (OPN) were significantly overexpressed in HS arteries. Fisher exact test and annotation-based gene subsets showed that genes upregulated by Jun and Ca 2ϩ /cAMP-response element-binding protein (CREB) were overrepresented. A model of cultured rat cerebrovascular smooth muscle cells was used to test the hypothesis that angiotensin II (ANG II), JunB, and CREB are important in the regulation of genes identified in the rat hypertension model. ANG II induced a transient induction of junB and a delayed induction of PAI-1 and OPN mRNA levels, which were reduced by ERK inhibition with U-0126. Silencing junB using small-interfering RNA reduced mRNA levels of OPN but not PAI-1. The silencing of CREB reduced PAI-1 induction by ANG II but enhanced the transcription of OPN. Together, these results suggest that salt-induced hypertensive disease promotes changes in matricellular genes that are stimulated by ANG II, regulated by ERK, and selectively regulated by JunB and CREB. microarray; Dahl rat; brain arteries; mitogen-activated protein kinase signaling; transcription factors HYPERTENSION IS A multifactorial disease, linked to both genetic and environmental origins, that ultimately causes direct alterations on the vasculature including smooth muscle cell proliferation and vascular remodeling (2, 34, 48). Rats selectively bred for hypertension studies have been useful models to study the complexity of human essential hypertension (42). The Dahl salt-sensitive (Dahl S) genetic model of hypertension is a paradigm of low renin hypertension observed in humans. Two genetic defects have been identified in the Dahl S strain including a mutation of the ␣ 1 Na ϩ , K ϩ -ATPase gene, affecting the renal basolateral epithelia throughout the nephron, and a restriction fragment-length polymorphism in the renin gene, affecting the proximal tubule (19,44).In response to the Na ϩ challenge of a high-...

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Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure

2000

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Adult cardiac myocytes are terminally differentiated cells that are no longer able to divide. Accumulating data support the idea that apoptosis in these cells is involved in the transition from cardiac compensation to decompensated heart failure. Since a number of neurohormonal factors are activated in this state, these factors may be involved in the positive and negative regulation of apoptosis in cardiac myocytes. beta1-Adrenergic receptor and angiotensin type 1 receptor pathways, nitric oxide and natriuretic peptides are involved in the induction of apoptosis in these cells, while alpha1- and beta2-adrenergic receptor and endothelin-1 type A receptor pathways and gp130-related cytokines are antiapoptotic. The myocardial protection of the latter is mediated, at least in part, through mitogen-activated protein kinase-dependent pathways, compatible with the findings in other cell types. In contrast, signaling pathways leading to apoptosis in cardiac myocytes are distinct from those in other cell types. The cAMP/PKA pathway induces apoptosis in cardiac myocytes and blocks apoptosis in other cell types. The p300 protein, a coactivator of p53, mediates apoptosis in fibroblasts but appears to play a protective role in differentiated cardiac myocytes. The inhibition of myocardial cell apoptosis in heart failure may be achieved by directly blocking apoptosis signaling pathways or by modulating neurohormonal factors involved in their regulation. These may provide novel therapeutic strategies in some forms of heart failure.

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Cardiac Endothelin-1 Plays a Critical Role in the Functional Deterioration of Left Ventricles During the Transition From Compensatory Hypertrophy to Congestive Heart Failure in Salt-Sensitive Hypertensive Rats

Cited by 142 publications

References 52 publications

Reinduction of T-Type Calcium Channels by Endothelin-1 in Failing Hearts In Vivo and in Adult Rat Ventricular Myocytes In Vitro

Reinduction of T-Type Calcium Channels by Endothelin-1 in Failing Hearts In Vivo and in Adult Rat Ventricular Myocytes In Vitro

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB

Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure

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