Relationship between the Effect on Calcium Turnover and Early Cardiotoxicity of Doxorubicin and 4'-EPI-Doxorubicin in Guinea Pig Heart Muscle

1980 ◽  
Vol 66 (6) ◽  
pp. 689-697 ◽  
Author(s):  
Fabrizio Villani ◽  
Luigia Favalli ◽  
Francesco Piccinini
Keyword(s):  
Guinea Pig ◽  
Heart Muscle ◽  
Myocardial Contractility ◽  
Negative Inotropic Effect ◽  
Experimental Models ◽  
Inotropic Effect ◽  
General Mechanism ◽  
Guinea Pig Heart ◽  
Membrane Bound ◽  
Guinea Pig Atria

Doxorubicin and 4'-epi-doxorubicin, two anthracycline derivatives with different cardiotoxic effects in experimental models, were found to decrease myocardial contractility in isolated guinea pig atria by significantly modifying calcium turnover. This effect seems to be mainly localized on the fast exchanging membrane-bound calcium, while these drugs do not significantly influence the intracellular stores of calcium. 4'-epi-doxorubicin, which induces a less negative inotropic effect than doxorubicin, produces a smaller inhibition of calcium turnover. This supports the hypothesis that the inhibition of calcium turnover and particularly of the fast exchanging calcium compartment is a general mechanism involved in the early anthracycline-induced cardiotoxicity.

Functional and autoradiographic characterization of dopamine D2-like receptors in the guinea pig heart

2002 ◽  
Vol 80 (6) ◽  
pp. 578-587 ◽  
Author(s):  
María de Jesús Gómez ◽  
Guy Rousseau ◽  
Réginald Nadeau ◽  
Roberto Berra ◽  
Gonzalo Flores ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Western Blot ◽  
Dopamine Receptors ◽  
Negative Inotropic Effect ◽  
Cyclase Activity ◽  
Inotropic Effect ◽  
Receptor Subtypes ◽  
Guinea Pig Heart ◽  
Additional Information ◽  
The Right

Dopamine receptors include the D1- (D1 and D5 subtypes) and D2-like (D2, D3, and D4 subtypes) families. D1-like receptors are positively and D2-like receptors negatively coupled to the adenylyl cyclase. Dopamine D2-like (D4 subtype) receptors have been identified in human and rat hearts. However the presence of D2 and D3 receptor subtypes is unclear. Furthermore, their role in cardiac functions is unknown. By autoradiographic studies of guinea pig hearts, we identified D3 and D4 receptors, using the selective radioligands [3H]-7-OH-DPAT and [3H]emonapride (YM-09151-2 plus raclopride). Western blot analysis confirmed D3 and D4 receptors in the right and left ventricle of the same species. Selective agonists of D3 and D4 receptors (±)-7-OH-DPAT and PD 168 077 (10–9 to 10–5 M, respectively) induced a significant negative chronotropic and inotropic effect in the isolated guinea pig heart preparation. Negative inotropic effect induced by PD 168 077 was associated with an inhibition in cyclase activity. No changes in cyclase activity were found with (±)-7-OH-DPAT. The aim of this study is to support the presence of D3 and D4 receptors in the heart. Although our results suggest that D3 and D4 receptors are functionally active in the heart, we need additional information with an antagonist and an agonist of improved potency and selectivity to understand the respective roles of D3 and D4 receptors in the cardiac functions.Key words: Dopamine receptors (D2, D3, D4 subtypes), autoradiography, Western blot, cAMP, heart.

scholarly journals Potentiation of the negative inotropic effect of adenosine on guinea pig atria by cinepazide.

1980 ◽  
Vol 30 ◽  
pp. 133
Author(s):  
Hideki Moritoki ◽  
Shinji Fujita ◽  
Masao lakei ◽  
Yukio Ishida ◽  
Akira Akashi
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Atria

The Negative Inotropic Effect of β3-Adrenoceptor Stimulation in the Beating Guinea Pig Heart

2000 ◽  
Vol 35 (5) ◽  
pp. 786-790 ◽  
Author(s):  
Tetsuya Kitamura ◽  
Katsuya Onishi ◽  
Kaoru Dohi ◽  
Tsutomu Okinaka ◽  
Naoki Isaka ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Heart

scholarly journals Negative Inotropic Effect of Diazepam in Isolated Guinea Pig Heart.

2001 ◽  
Vol 63 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Yukio HARA ◽  
Hiroe KOBAYASHI ◽  
Satomi OOSHIRO ◽  
Keisuke FUTAMURA ◽  
Takeshi NISHINO ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Heart

scholarly journals POTENTIATION BY DILAZEP OF THE NEGATIVE INOTROPIC EFFECT OF ADENOSINE ON GUINEA-PIG ATRIA

1980 ◽  
Vol 68 (2) ◽  
pp. 343-349 ◽  
Author(s):  
SHINJI FUJITA ◽  
YUKIO ISHIDA ◽  
KYOKO IZUMI ◽  
HIDEKI MORITOKI ◽  
MASAYUKI OHARA ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Atria

Roles of PKA, PI3K, and cPLA2 in the NO-mediated negative inotropic effect of β2-adrenoceptor agonists in guinea pig right papillary muscles

2008 ◽  
Vol 294 (1) ◽  
pp. C106-C117 ◽  
Author(s):  
Fabien A. Faucher ◽  
François E. Gannier ◽  
Jacques M. Lignon ◽  
Pierre Cosnay ◽  
Claire O. Malécot
Keyword(s):  
Guinea Pig ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Guinea Pig Heart ◽  
Inotropic Effects ◽  
Inotropic State ◽  
No Release ◽  
High Concentrations

Although β2-adrenoceptors represent 15–25% of β-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of β2-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, −5% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 μM) due to activation of β1-adrenoceptors. In the presence of 4 μM atenolol, the concentration-dependent NIE (−12% at 6 μM) was biphasic, best described by a double logistic equation with respective EC50 values of 3 and ∼420 nM, and was insensitive to SR59230A. In muscles from pertussis toxin-treated guinea pigs, the salbutamol-induced positive inotropic effect was sensitive to low concentrations of ICI-118551 in an unusual manner. Experiments in reserpinized animals revealed the importance of the phosphorylation-dephosphorylation processes. PKA inhibition reduced and suppressed the effects obtained at low and high concentrations, respectively, indicating that its activation was a prerequisite to the NIE. The effect occurring at nanomolar concentrations depended upon PKA/phosphatidylinositol 3-kinase/cytosolic phospholipase A2 (cPLA2) activations leading to nitric oxide (NO) release via the arachidonic acid/cyclooxygenase pathway. NO release via PKA-dependent phosphorylation of the receptor was responsible for the inotropic effect observed at submicromolar concentrations, which is negatively controlled by cPLA2. The possibility that these effects are due to an equilibrium between different affinity states of the receptor (Gs/Gi coupled and Gi independent with different signaling pathways) that can be displaced by ICI-118551 is discussed. We conclude that β2-adrenoceptors are functional in guinea pig heart and can modulate the inotropic state.

Effects of inotropic agents on isolated guinea pig heart under conditions that modify calcium pools involved in contractile activation

1986 ◽  
Vol 64 (7) ◽  
pp. 947-953 ◽  
Author(s):  
Kyosuke Temma ◽  
Tai Akera ◽  
Yuk-Chow Ng
Keyword(s):  
Guinea Pig ◽  
Heart Muscle ◽  
Isolated Heart ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Common Mechanism ◽  
Primary Role ◽  
Guinea Pig Heart ◽  
Inotropic Effects ◽  
Contractile Activation

Positive inotropic effects of strophanthidin were compared with those of isoproterenol, BAY K 8644, grayanotoxin, veratridine, and monensin in electrically stimulated left atrial muscle preparations of guinea pig heart under conditions in which the calcium pool, playing a primary role in contractile activation, was altered. In concentrations that caused similar degrees of increase in developed tension under 1 Hz stimulation, grayanotoxin and strophanthidin caused a relatively large increase in potentiated postrest contraction compared with that caused by isoproterenol, whereas the effect of BAY K 8644 on the postrest contraction was the smallest. The effect of high concentrations of grayanotoxin or strophanthidin, however, resembled that of isoproterenol. The sensitivity of the isolated heart muscle to these agents was compared under conditions in which utilization of various calcium pools contributing to contractile activation was suppressed. Mn2+, which reduces contribution of very superficial Ca2+, reduced sensitivity of heart muscle to the positive inotropic effect of isoproterenol and enhanced the inotropic effect of monensin or veratridine. Verapamil, nifedipine, diltiazem, or ryanodine did not have marked effects on the positive inotropic action of Ca2+, monensin, veratridine, or strophanthidin. These results suggest that the positive inotropic actions of veratridine, grayanotoxin, and strophanthidin share a common mechanism and that low concentrations of strophanthidin may increase loading of Ca2+ pool, which plays an important role in potentiated postrest contraction.

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