Overexpression of diacylglycerol kinase ζ inhibits endothelin-1-induced decreases in Ca2+ transients and cell shortening in mouse ventricular myocytes

Blockade of L-type Ca2+ channels in spontaneously contracting cultured neonatal rat ventricular myocytes causes contractile arrest, myofibrillar disassembly, and accelerated myofibrillar protein turnover. To determine whether myofibrillar protein turnover. To determine whether myofibrillar atrophy results indirectly from loss of mechanical signals or directly from alterations in intracellular Ca2+ concentration ([Ca2+]i), contractile activity was inhibited with verapamil (10 microM) or 2,3-butanedione monoxime (BDM), and their effects on cell shortening, [Ca2+]i, and myosin heavy chain (MHC) turnover were assessed. Control cells demonstrated spontaneous [Ca2+]i transients (peak amplitude 232 +/- 15 nM, 1-2 Hz) and vigorous contractile activity. Verapamil inhibited shortening by eliminating spontaneous [Ca2+]i transients. Low concentrations of BDM (5.0-7.5 mM) had no effect on basal or peak [Ca2+]i transient amplitude but reduced cell shortening, whereas 10 mM BDM reduced both [Ca2+]i transient amplitude and shortening. Both agents inhibited MHC synthesis, but only verapamil accelerated MHC degradation. Thus MHC half-life does not change in parallel with contractile activity but rather more closely follows changes in [Ca2+]i. [Ca2+]i transients appear critical in maintaining myofibrillar assembly and preventing accelerated MHC proteolysis.

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Modulation of the Na+/Ca2+ Exchanger by Isoprenaline, Adenosine, and Endothelin-1 in Guinea Pig Ventricular Myocytes

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2002.tb04789.x ◽

2006 ◽

Vol 976 (1) ◽

pp. 535-538 ◽

Cited By ~ 2

Author(s):

YIN HUA ZHANG ◽

ANNABEL K. HINDE ◽

ANDREW F. JAMES ◽

JULES C. HANCOX

Keyword(s):

Guinea Pig ◽

Ventricular Myocytes ◽

Endothelin 1

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Effects of EMD 53998 and its enantiomcrs on cell shortening and Ca2+ transients in indo-1 loaded rabbit ventricular myocytes

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)45447-4 ◽

1997 ◽

Vol 73 ◽

pp. 236

Author(s):

Hiromi Sugawara ◽

Tomoo Watanabe ◽

Masao Endoh

Keyword(s):

Ventricular Myocytes ◽

Cell Shortening ◽

Rabbit Ventricular Myocytes ◽

Emd 53998

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Role of cyclooxygenase in ventricular effects of adrenomedullin: is adrenomedullin a double-edged sword in sepsis?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00337.2003 ◽

2004 ◽

Vol 286 (3) ◽

pp. H1034-H1042 ◽

Cited By ~ 19

Author(s):

Shivani Mittra ◽

Jean-Marc Hyvelin ◽

Qixian Shan ◽

Fai Tang ◽

Jean-Pierre Bourreau

Keyword(s):

Cardiac Tissue ◽

Ventricular Myocytes ◽

Marked Decrease ◽

Negative Inotropic Effect ◽

Inotropic Effect ◽

Prolonged Incubation ◽

Cell Contractility ◽

Rat Ventricular Myocytes ◽

Cell Shortening ◽

Cox Inhibitor

Adrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions. However, the direct inotropic effect of ADM on normal and compromised cardiomyocytes is not clear. In rat ventricular myocytes, ADM produced an initial (<30 min) increase in cell shortening and Ca2+ transient and, on prolonged incubation (>1 h), a marked decrease in cell shortening and Ca2+ transient. Both effects were sensitive to inhibition by the ADM antagonist ADM-(22–52). The increase and decrease in cell shortening and Ca2+ transient were attenuated by pretreatment with indomethacin [a nonspecific cyclooxygenase (COX) inhibitor], nimesulide and SC-236 (specific COX-2 inhibitors), and tranylcypromine (a prostacyclin synthase inhibitor); SQ-29548 (a thromboxane receptor antagonist) was without effect. Cells isolated from LPS-treated rats that were in the late, hypodynamic phase of septic shock also showed a marked decrease in cell shortening and Ca2+ transient. Because ADM is overexpressed in sepsis, we repeated the above protocol in cells isolated from LPS-treated rats. At 4 h after LPS injection, ADM levels markedly increased in plasma, ventricles, and freshly isolated ventricular myocytes. Decreases in cell shortening and Ca2+ transient in LPS-treated cells were reversed by pretreatment with ADM-(22–52). Anti-ADM (rat) IgG also reversed the decrease in cell shortening and other parameters of cell kinetics. Indomethacin, SC-236, and tranylcypromine restored cell contractility and the decrease in Ca2+ transient, whereas SQ-29548 had no effect, implying that prostacyclin played a role in both effects. However, with regard to cell-shortening kinetics, indomethacin and SQ-29548 decreased the amount of time taken by the cells to return to baseline, whereas SC-236 and tranylcypromine did not, implying that not only prostacyclin, but also thromboxane, is involved. The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes.

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Increased endothelin-1 and endothelin receptor expression in myocytes of ischemic and reperfused rat hearts and ventricular myocytes exposed to ischemic conditions and its inhibition by nitric oxide generation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y03-030 ◽

2003 ◽

Vol 81 (2) ◽

pp. 105-113 ◽

Cited By ~ 18

Author(s):

Xiaohong Tracey Gan ◽

Subrata Chakrabarti ◽

Morris Karmazyn

Keyword(s):

Nitric Oxide ◽

Mrna Expression ◽

Ventricular Myocytes ◽

Receptor Expression ◽

Neonatal Rat ◽

No Donor ◽

Myocardial Ischemia And Reperfusion ◽

Endothelin 1 ◽

Hypoxic Conditions ◽

Rat Hearts

Endothelin-1 (ET-1) and nitric oxide (NO) exert opposite effects in the cardiovascular system, and there is evidence that the NO counters the potential deleterious effects of ET-1. We investigated whether NO affects the increased mRNA expression of ET-1 and endothelin receptors induced by (i) 30 min of ischemia with or without 30 min reperfusion in myocytes from isolated rat hearts or (ii) ischemic conditions (acidosis or hypoxia) in cultured rat neonatal ventricular myocytes. Ischemia with or without reperfusion produced more than a twofold increase in mRNA expression of ET-1 as well as the ETAand ETBreceptor (P < 0.05), although these effects were completely blocked by the NO donor 3-morpholinosydnonimine (SIN-1; 1 μM). To assess the possible factors regulating ET expression, myocytes were exposed to acidosis (pH 6.86.2) or to hypoxic conditions in an anaerobic chamber for 24 h in the presence or absence of SIN-1. At all acidic pHs, ET-1 and ETAreceptor mRNA expression was significantly (P < 0.05) elevated approximately threefold, although the magnitude of elevation was independent of the degree of acidosis. These effects were completely prevented by SIN-1. ETBreceptor expression was unaffected by acidosis. Hypoxia increased ET-1 as well as ETAand ETBreceptor expression threefold (P < 0.05), although this was unaffected by SIN-1. Our results demonstrate that myocardial ischemia and reperfusion upregulate the ET system, which is inhibited by NO. Although increased expression of the ET system can be mimicked by both acidosis and hypoxia, only the effects of the former are NO sensitive. NO may serve an endogenous inhibitory factor which regulates the expression of the ET system under pathological conditions.Key words: ET-1, ET receptors, NO, neonatal rat ventricular myocytes, hypoxia, acidosis.

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Endothelin-1 inhibitsl-type Ca currents enhanced by isoproterenol in guinea-pig ventricular myocytes

Pflügers Archiv - European Journal of Physiology ◽

10.1007/bf02191900 ◽

1996 ◽

Vol 431 (4) ◽

pp. 533-539 ◽

Cited By ~ 15

Author(s):

Lai-Hua Xie ◽

Minoru Horie ◽

Andrew F. James ◽

Masato Watanuki ◽

Shigetake Sasayama

Keyword(s):

Guinea Pig ◽

Ventricular Myocytes ◽

Endothelin 1 ◽

Ca Currents

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Cyclic stretch and endothelin-1 mediated activation of chloride channels in cultured neonatal rat ventricular myocytes

Clinical Science ◽

10.1042/cs103s148s ◽

2002 ◽

Vol 103 (s2002) ◽

pp. 148S-151S ◽

Cited By ~ 7

Author(s):

Henriëtte W. DE JONGE ◽

Dick H.W. DEKKERS ◽

Ben C. TILLY ◽

Jos M.J. LAMERS

Keyword(s):

Ventricular Myocytes ◽

Cyclic Stretch ◽

Neonatal Rat ◽

Rat Cardiomyocytes ◽

Basal Rate ◽

Rat Ventricular Myocytes ◽

Endothelin 1 ◽

Cl Channel ◽

Cl Channels ◽

Neonatal Rat Ventricular Myocytes

To date various types of Cl- currents have been recorded in cardiac myocytes from different regions of the heart and from different species. Most of these are silent under basal conditions, but are rapidly activated under the influence of various agonists or physical stress that, in the long term, also lead to development of hypertrophy. Previously, we identified three different Cl- channel activities in neonatal rat cardiomyocytes: (i) Ca2+ regulated, (ii) cAMP regulated (cystic fibrosis transmembrane conductance regulator Cl- channels) and (iii) osmoregulated Cl- channels. In this study, we examined comparatively the effects of cyclic stretch and endothelin-1 (ET-1) on Cl- channel activity in primary cultures of neonatal rat ventricular myocytes using an 125I-efflux assay. About 4min after the start of the 125I-efflux (mean basal rate amounts 6.3% of total 125I incorporated/min), the addition of 10nM ET-1 or the application of cyclic stretch rapidly and transiently increased 125I-efflux by 3.8%/min and 0.8%/min respectively above the basal rate. The stretch induced 125I-efflux rate could be blocked by 100µM Gd3+ but it had no effect on the ET-1 response. After 24h stimulation by ET-1 or cyclic stretch the myocytes responded by hypertrophy which is detected by increases of 3H-leucine incorporation into protein and protein/DNA ratio. In conclusion, cyclic stretch as well as ET rapidly and transiently activate Cl- channels in rat neonatal cardiomyocytes. The results suggest that the activation of distinct types of Cl- channels (co)transduce the stretch- and agonist-induced hypertrophic responses in these myocytes.

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