Negative Inotropic Effect of Adrenomedullin in Isolated Adult Rabbit Cardiac Ventricular Myocytes

Circulation ◽  
1997 ◽  
Vol 95 (9) ◽  
pp. 2318-2324 ◽  
Author(s):  
Hiroshi Ikenouchi ◽  
Kenji Kangawa ◽  
Hisayuki Matsuo ◽  
Yasunobu Hirata
Keyword(s):  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Adult Rabbit ◽  
Cardiac Ventricular Myocytes

Effects of TNF-alpha on [Ca2+]i and contractility in isolated adult rabbit ventricular myocytes

1996 ◽  
Vol 271 (4) ◽  
pp. H1449-H1455 ◽  
Author(s):  
J. I. Goldhaber ◽  
K. H. Kim ◽  
P. D. Natterson ◽  
T. Lawrence ◽  
P. Yang ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Cell Length ◽  
Inotropic Effect ◽  
Tnf Alpha ◽  
Adult Rabbit ◽  
Cell Shortening ◽  
Rabbit Ventricular Myocytes ◽  
In Cells

The mechanism of the acute negative inotropic effect of tumor necrosis factor-alpha (TNF-alpha) was studied in enzymatically isolated adult rabbit ventricular myocytes. In cells loaded with fura 2 acetoxymethyl ester (AM) and paced intermittently at 0.2 Hz, TNF-alpha at doses < or = 10,000 U/ml caused a significant reduction in active cell shortening at 20 min, without reducing the amplitude of the accompanying intracellular Ca2+ concentration ([Ca2+]i) transient. Similar results were obtained in cells loaded with indo 1-AM and paced continuously at 0.2 Hz during exposure to TNF-alpha (10,000 U/ml). The effect of TNF-alpha on cell shortening could be prevented by the nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME) but not its inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). The NO scavenger hemoglobin also attenuated the effects of TNF-alpha. TNF-alpha also caused a significant increase in diastolic cell length without any change in diastolic [Ca2+]i. The effect on cell length was prevented by L-NAME but not D-NAME. In cells loaded with the pH indicator seminaphthorhodafluor-AM, TNF-alpha did not alter pH sufficiently to account for the negative inotropic effect. These data suggest that high doses of TNF-alpha can acutely induce NO synthesis in isolated myocytes and reduce contractility by decreasing myofilament [Ca2+]i responsiveness. The mechanism of this altered myofilament [Ca2+]i response is unknown but does not appear to be pH mediated.

scholarly journals Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect

2014 ◽  
Vol 104 (3) ◽  
pp. 456-466 ◽  
Author(s):  
Luis Alberto Gonano ◽  
Malena Morell ◽  
Juan Ignacio Burgos ◽  
Raul Ariel Dulce ◽  
Verónica Celeste De Giusti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Nitric Oxide Release ◽  
Hypotonic Swelling ◽  
Cardiac Ventricular Myocytes

Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes

1993 ◽  
Vol 265 (3) ◽  
pp. H793-H800 ◽  
Author(s):  
O. Kohmoto ◽  
H. Ikenouchi ◽  
Y. Hirata ◽  
S. Momomura ◽  
T. Serizawa ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Neonatal Rat ◽  
Inotropic Effect ◽  
Adult Rabbit ◽  
Free Calcium ◽  
Intracellular Acidosis ◽  
Cell Contraction ◽  
Endothelin 1 ◽  
Free Calcium Concentration

We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species.

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

2004 ◽  
Vol 286 (3) ◽  
pp. H1034-H1042 ◽  
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.

Gs and Gi coupling of adrenomedullin in adult rat ventricular myocytes

2006 ◽  
Vol 290 (5) ◽  
pp. H1842-H1847 ◽  
Author(s):  
Shivani Mittra ◽  
Jean-Pierre Bourreau
Keyword(s):  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Paracrine Factor ◽  
Inotropic Effects ◽  
Prolonged Incubation ◽  
Rat Ventricular Myocytes ◽  
Cell Shortening ◽  
Adult Rat

Adrenomedullin (ADM) acts as an autocrine or a paracrine factor in the regulation of cardiac function. The intracellular mechanisms involved in the direct effect of ADM on adult rat ventricular myocytes (ARVMs) are still to be elucidated. In ARVMs from normal rats, ADM produced an initial (<30 min) increase in cell shortening and Ca2+ transients and a marked decrease in both on prolonged incubation (>1 h). Both effects were sensitive to ADM antagonist ADM-(22–52). Treatment with SQ-22536, an inhibitor of adenylate cyclase, blocked the positive inotropic effect of ADM and potentiated its negative inotropic effect. The negative inotropic effect was sensitive to inhibition by pertussis toxin (PTX), an inhibitor of Gi proteins and KT-5720, an inhibitor of PKA. The observations suggest a switch from Gs-coupled to PTX-sensitive, PKA-dependent Gi coupling by ADM in ARVMs. The ADM-mediated Gi-signaling system involves cAMP-dependent pathways because SQ-22536 further increased the negative inotropic actions of ADM. Also, because ADM is overproduced by ARVMs in our rat model of septic shock, ARVMs from LPS-treated rats were subjected to treatment with ADM-(22–52) and PTX. The decrease in cell shortening and Ca2+ transients in LPS-treated ARVMs could be reversed back with ADM-(22–52) and PTX. This indicates that ADM plays a role in mediating the negative inotropic effect in LPS-treated ARVM through the activation of Gi signaling. This study delineates the intracellular pathways involved in ADM-mediated direct inotropic effects on ARVMs and also suggests a role of ADM in sepsis.

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