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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

Published on Nov 18, 2003in Circulation23.054
· DOI :10.1161/01.CIR.0000096484.03318.AB
Toshiaki Izumi12
Estimated H-index: 12
(Kyoto University),
Yasuki Kihara40
Estimated H-index: 40
(Kyoto University)
+ 7 AuthorsAkinori Noma37
Estimated H-index: 37
(Kyoto University)
Abstract
Background— In ventricular myocardium, the T-type Ca2+ current (ICa,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 ICa,T (measured in the freshly isolated LV myocytes) nor an increase in α-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, ICa,T was recorded in most of the cells (−0.87±0.18 pA/pF at −30 mV, P<0.01 versus LVH). This was associate...
  • References (29)
  • Citations (63)
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References29
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#1Yoshitaka IwanagaH-Index: 30
#2Yasuki KiharaH-Index: 40
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Background In view of their mutual crosstalk, the roles of angiotensin II (Ang II) and endothelin-1 (ET-1) in the myocardium are assumed to be synergistic and supplemental. Methods and Results In the phase of compensated left ventricular (LV) hypertrophy of Dahl salt-sensitive rats, Ang II peptide and the ACE mRNA in the LV were increased by 1.6- and 3.8-fold, respectively. In contrast, ET-1 peptide and the preproET-1 mRNA remained unchanged. In subsequent congestive heart failure (CHF), Ang II ...
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#1Wataru Hayashida (Kyoto University)H-Index: 11
#2Yasuki Kihara (Kyoto University)H-Index: 40
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Mitogen-activated protein kinases (MAPKs) are involved in the early development of cardiac hypertrophy, but their roles in chronic left ventricular hypertrophy (LVH) are unclear. We studied the angiotensin (Ang) II-induced cardiac MAPK activation of the hypertensive Dahl salt-sensitive (DS) rats in the subacute developing LVH stage, the chronic compensated LVH stage, and the congestive heart failure (CHF) stage. In the isolated, coronary-perfused heart preparation, Ang II infusion (1×10−6mol/l) ...
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Abstract The expression of endothelin-1 (ET-1) in cardiac myocytes is markedly induced during the development of heart failurein vivo and by stimulation with the α1-adrenergic agonist phenylephrine in culture. Although recent studies have suggested a role for cardiac-specific zinc finger GATA factors in the transcriptional pathways that modulate cardiac hypertrophy, it is unknown whether these factors are also involved in cardiac ET-1 transcription and if so, how these factors are modulated duri...
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