Effect of adenosine on the cardiac actions of prostaglandins E2, I2, and F2α

1982 ◽  
Vol 60 (6) ◽  
pp. 819-824 ◽  
Author(s):  
Morris Karmazyn ◽  
Naranjan S. Dhalla

Previous reports have demonstrated an antagonistic influence of adenosine on the biological effects of prostaglandins (PGs). We examined such a possible relationship on the isolated rat heart perfused at constant pressure and maintained at a constant heart rate. PGE2 and PGF2α (2.8 × 10−11 to 2.8 × 10−7 M) exerted a positive inotropic influence on the heart with PGF2α demonstrating the greater maximum effect. PGI2 had a negative inotropic effect only at high concentrations (2.8 × 10−9 to 2.8 × 10−7 M). The coronary flow was decreased by both PGE2 and PGF2α. The concentrations of PGI2 employed had minimal vasoactive properties (20% increase in flow at 2.9 × 10−7 M). Adenosine at concentrations which increased coronary flow by 24 to 63% (0.1 to 10 μM) had no influence on either the alteration in contractile force produced by PGE2, PGF2α, or PGI2 or on the coronary effects of PGE2, or PGI2. Adenosine did however, attenuate the degree of coronary flow reduction produced by PGF2α administration. These results are suggestive of a selective inhibiting influence of adenosine on the coronary constricting effects of PGF2α in the isolated rat heart.

1991 ◽  
Vol 69 (11) ◽  
pp. 1705-1712 ◽  
Author(s):  
Noburu Konno ◽  
K. J. Kako

Hydrogen peroxide (H2O2) and hypochlorite (HOCl) cause a variety of cellular dysfunctions. In this study we examined the effects of these agents on the electrical potential gradient across the inner membrane of mitochondria in situ in isolated rat heart myocytes. Myocytes were prepared by collagenase digestion and incubated in the presence of H2O2 or HOCl. Transmembrane electrical gradients were measured by distribution of [3H]triphenylmethylphosphonium+, a lipophilic cation. The particulate fraction was separated from the cytosolic compartment first by permeabilization using digitonin, followed by rapid centrifugal sedimentation through a bromododecane layer. We found that the mitochondrial membrane potential (161 ± 7 mV, negative inside) was relatively well maintained under oxidant stress, i.e., the potential was decreased only at high concentrations of HOCl and H2O2 and gradually with time. The membrane potential of isolated rat heart mitochondria was affected similarly by H2O2 and HOCl in a concentration- and time-dependent manner. High concentrations of oxidants also reduced the cellular ATP level but did not significantly change the matrix volume. When the extra-mitochondrial free calcium concentration was increased in permeabilized myocytes, the transmembrane potential was decreased proportionally, and this decrease was potentiated further by H2O2. These results support the view that heart mitochondria are equipped with well-developed defense mechanisms against oxidants, but the action of H2O2 on the transmembrane electrical gradient is exacerbated by an increase in cytosolic calcium. Keywords: ATP, calcium, cardiomyocyte, cell defense, mitochondrial membrane potential, oxidant, triphenylmethylphosphonium.


1999 ◽  
Vol 276 (6) ◽  
pp. H2076-H2084 ◽  
Author(s):  
Robert D. Lasley ◽  
Prakash Narayan ◽  
M. Salik Jahania ◽  
Elizabeth L. Partin ◽  
Kathleen R. Kraft ◽  
...  

The purpose of this study was to compare the hemodynamic effects of the adenosine A3-receptor agonists N 6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-β-d-ribofuranosyl]adenine (IB-MECA) and 2-chloro- N 6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-β-d-ribofuranosyl]adenine (Cl-IB-MECA) in isolated rat and rabbit hearts and in the intact, open-chest pig. Isolated hearts perfused with Krebs-Henseleit buffer at a constant pressure (70 mmHg) were treated with 50 nM of either IB-MECA or Cl-IB-MECA. Neither IB-MECA nor Cl-IB-MECA altered ventricular function or heart rate in the isolated rat and rabbit hearts, and neither agent altered coronary flow in the rabbit. However, 2 min of IB-MECA treatment in the isolated rat heart increased coronary flow by 25%, an effect that did not exhibit tachyphylaxis. The IB-MECA-induced coronary dilation was only partially attenuated by the adenosine A3-receptor antagonist MRS-1191 (50 nM). IB-MECA-induced coronary dilation was completely blocked by the adenosine A2a-receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (Sch-58261, 50 nM). Cl-IB-MECA (50 nM) did not increase coronary flow in the rat, but 100 nM did increase flow by 18%. In pentobarbital sodium-anesthetized pigs IB-MECA (5 μg/kg iv) decreased systemic blood pressure and increased pulmonary artery pressure, effects that did exhibit tachyphylaxis. These results illustrate that adenosine A3-receptor agonists produce species-dependent effects, which in the rat heart appear to be caused by adenosine A2a-receptor activation.


2018 ◽  
Vol 37 (05) ◽  
pp. 515-525 ◽  
Author(s):  
I. M. Stojic ◽  
V. Lj. Jakovljevic ◽  
V. I. Zivkovic ◽  
I. M. Srejovic ◽  
T. R. Nikolic ◽  
...  

Cardiology ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 238-248 ◽  
Author(s):  
Haywood Blum ◽  
Tamas Ivanics ◽  
Danning Zhang ◽  
Krzysztof Wroblewski ◽  
Mary D. Osbakken

1993 ◽  
Vol 264 (3) ◽  
pp. H783-H790 ◽  
Author(s):  
C. Ibuki ◽  
D. J. Hearse ◽  
M. Avkiran

Transient (2 min) acidic (pH 6.6) reperfusion with low [HCO3-] solution suppresses reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart. Using this preparation, we tested whether the effect was mediated by the high [H+] or the low [HCO3-] of perfusate. Left and right coronary beds were independently perfused with HCO3(-)-containing (25.0 mmol/l) solution at pH 7.4. Regional ischemia was then induced by stopping flow to the left coronary bed for 10 min. Hearts were subsequently assigned to four groups (n = 12 hearts/group), and the left coronary bed was reperfused with either HCO3(-)-containing (25.0 or 4.0 mmol/l) or HCO3(-)-free (5.0 mmol/l HEPES) solution, at pH 7.4 throughout (control reperfusion) or at pH 6.6 for the first 2 min and at pH 7.4 from 2 to 5 min (acidic reperfusion). Regardless of the buffer, controls exhibited a high (92 and 100%) incidence of VF; this was reduced to 42% in both of the acidic reperfusion groups (P < 0.05). There were no intergroup differences in heart rate, coronary flow, or size of ischemic zone. Thus high [H+], rather than low [HCO3-], appears to mediate the antifibrillatory effect of transient acidic reperfusion.


1976 ◽  
Vol 41 (4) ◽  
pp. 603-607 ◽  
Author(s):  
M. A. Duvelleroy ◽  
M. Duruble ◽  
J. L. Martin ◽  
B. Teisseire ◽  
J. Droulez ◽  
...  

We describe a method for perfusion of a working isolated rat heart with washed erythrocytes suspended in a Krebs-Henseleit bicarbonate buffer containing bovine albumin (fraction V). With washed pig red cells, as hematocritwas varied between 0 and 40%, coronary flow (CF), aortic flow (AF), external work (W), and myocardial oxygen consumption (MVO2) were measured. Hemodynamic data at a hematocrit of 30% (CF = 5.4 +/- 0.7 ml/min per g, AF = 75 +/- 8 ml/min per g) were identical with those reported for the intact animal.Coronary sinus PO2 was highest with a red cell-free perfusate suggesting that coronary flow is partially shunted. Human red cells obtained from bankedblood, were tried also with success. With careful filtration, the preparation is stable for 2 h and well suited for study of the dynamics of myocardial oxygen delivery.


Life Sciences ◽  
2002 ◽  
Vol 70 (10) ◽  
pp. 1121-1128 ◽  
Author(s):  
Alvair P. Almeida ◽  
Steyner F. Côrtes ◽  
Anderson J. Ferreira ◽  
Virgı́nia S. Lemos

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