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

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

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.

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.

Negative inotropic effect of bradykinin in porcine isolated atrial trabeculae: role of nitric oxide

2001 ◽  
Vol 19 (7) ◽  
pp. 1289-1293 ◽  
Author(s):  
Beril Tom ◽  
René de Vries ◽  
Pramod R. Saxena ◽  
A. H. Jan Danser
Keyword(s):  
Nitric Oxide ◽  
Negative Inotropic Effect ◽  
Inotropic Effect

Intermedin elicits a negative inotropic effect in rat papillary muscles mediated by endothelial-derived nitric oxide

2012 ◽  
Vol 302 (5) ◽  
pp. H1131-H1137 ◽  
Author(s):  
Ana Luísa Pires ◽  
Marta Pinho ◽  
Cristina Maria Sena ◽  
Raquel Seica ◽  
Adelino F. Leite-Moreira
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Receptor Antagonist ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
No Production ◽  
Papillary Muscles ◽  
Cgrp Receptor ◽  
Inotropic Action

Intermedin (IMD) is a novel vasoactive peptide from the calcitonin gene-related peptide (CGRP) implicated in cardiac regulation, yet the contractile effects of IMD remain controversial, since previous studies in vivo and isolated cardiomyocytes documented contradictory results. We hypothesized cardiac endothelial cells involvement in IMD modulation of cardiac function as an explanation for these opposing observations. With this in mind, we investigated the direct action of increasing concentrations of IMD (10−8 to 10−6M) on myocardial performance parameters in rat left ventricular (LV) papillary muscles with and without endocardial endothelium (EE) and in presence of receptor antagonists and intracellular pathways inhibitors. In LV papillary muscles with intact EE, IMD induced a concentration-dependent negative inotropic action (%decrease relative to baseline, at IMD concentration of 10−6M, active tension of 14 ± 4%, and maximum velocity of tension rise of 10 ± 4%). These effects were blunted by EE removal, AM receptor antagonist (AM22–52), and CGRP receptor antagonist (CGRP8–37). Additionally, nitric oxide (NO) synthase inhibition with NG-nitro-l-arginine (l-NAME) in muscles with and without EE and guanylyl cyclase inhibition with {1 H-[1,2,4]oxadiazole-[4,4-a]-quinoxalin-1-one} not only blunted the negative inotropic action of IMD but also unmasked IMD-positive inotropic effect dependent on CGRP receptor PKA activation. Western blot quantification of phosphorylated cardiac troponin I (P-cTnI) in IMD-treated papillary muscles revealed a significant increase in P-cTnI when compared with untreated muscles, while in l-NAME-pretreated papillary muscles IMD failed to increase P-cTnI. Finally, we found that stimulation of both EE and microvascular endothelial cells with IMD significantly increased NO production by 40 ± 3 and 38 ± 3%, respectively, suggesting the role of cardiac endothelial cells in NO production upon IMD stimulation. Our findings establish IMD negative inotropic effect in isolated myocardium due to NO/cGMP pathway activation with concomitant thin myofilament desensitization by increase in cTnI phosphorylation and provide a coherent explanation for the previously reported contradictory results.

Sign in / Sign up

Export Citation Format

Share Document