Prostacyclin-thromboxane interactions in the platelet-perfused in vitro heart

1981 ◽  
Vol 241 (1) ◽  
pp. H18-H25
Author(s):  
K. Schror ◽  
P. Kohler ◽  
M. Muller ◽  
B. A. Peskar ◽  
P. Rosen
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Human Platelets ◽  
Coronary Vascular Resistance ◽  
Guinea Pig Heart ◽  
Vascular Bed ◽  
Bioassay Data ◽  
Induced Changes ◽  
Thromboxane Formation

A preparation of an isolated platelet-perfused guinea pig heart is described, which was utilized to study prostacyclin-thromboxane interrelationships. Infusion of washed human platelets (4 X 10(8)/min) through the coronary vascular bed stimulated the vascular PGI2 production from 114 +/- 27 to 350 +/- 30 pg/ml (P less than 0.01) and was associated with a significant increase in platelet cAMP from 1.2 +/- 0.4 to 2.6 +/- 0.9 pmol/10(8) platelets (P less than 0.05). Administration of arachidonic acid (AA) (45 micrograms) to the system led to a further increase (eight- to ninefold) of PGI2 and yielded marked thromboxane formation (20-25 ng/ml). Treatment of the hearts with aspirin (1 mM) prevented the PGI2 formation and AA-induced increase in platelet cAMP. Treatment of platelets with aspirin prevented thromboxane formation but did not influence AA-induced changes in platelet cAMP and vascular PGI2 production. Bioassay data of PGI2 and rabbit aortic contracting substance gave results comparable to radioimmunoassay of 6-keto-PGF1 alpha and thromboxane B2. AA always decreased the coronary vascular resistance whether thromboxanes were formed or not.

Effects of Dipyrone on Prostaglandin Production by Human Platelets and Cultured Bovine Aortic Endothelial Cells

1983 ◽  
Vol 49 (02) ◽  
pp. 132-137 ◽  
Author(s):  
A Eldor ◽  
G Polliack ◽  
I Vlodavsky ◽  
M Levy
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Ionophore A23187 ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Aortic Endothelial

SummaryDipyrone and its metabolites 4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoan- tipyrine inhibited the formation of thromboxane A2 (TXA2) during in vitro platelet aggregation induced by ADP, epinephrine, collagen, ionophore A23187 and arachidonic acid. Inhibition occurred after a short incubation (30–40 sec) and depended on the concentration of the drug or its metabolites and the aggregating agents. The minimal inhibitory concentration of dipyrone needed to completely block aggregation varied between individual donors, and related directly to the inherent capacity of their platelets to synthesize TXA2.Incubation of dipyrone with cultured bovine aortic endothelial cells resulted in a time and dose dependent inhibition of the release of prostacyclin (PGI2) into the culture medium. However, inhibition was abolished when the drug was removed from the culture, or when the cells were stimulated to produce PGI2 with either arachidonic acid or ionophore A23187.These results indicate that dipyrone exerts its inhibitory effect on prostaglandins synthesis by platelets or endothelial cells through a competitive inhibition of the cyclooxygenase system.

In Vitro Incorporation and Metabolism of Icosapentaenoic and Docosahexaenoic Acids in Human Platelets - Effect on Aggregation

1986 ◽  
Vol 56 (01) ◽  
pp. 057-062 ◽  
Author(s):  
Martine Croset ◽  
M Lagarde
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Fatty Acid Distribution ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Aggregation Response ◽  
Docosahexaenoic Acids ◽  
Membrane Level

SummaryWashed human platelets were pre-loaded with icosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or EPA + DHA and tested for their aggregation response in comparison with control platelets. In fatty acid-rich platelets, an inhibition of the aggregation could be observed when induced by thrombin, collagen or U-46619. The strongest inhibition was observed with DHA-rich platelets and it was reduced when DHA was incorporated in the presence of EPA.Study of fatty acid distribution in cell lipids after loading showed that around 90% of EPA or DHA taken up was acylated into phospholipids and a very small amount (less than 2%) remained in their free and hydroxylated forms. DHA was more efficiently acylated into phosphatidylethanolamine (PE) than into phosphatidylinositol (PI) in contrast to what observed with EPA, and both acids were preferentially incorporated into phosphatidylcholine (PC). EPA inhibited total incorporation of DHA and increased its relative acylation into PE at the expense of PC. In contrast, DHA did not affect the acylation of EPA. Upon stimulation with, thrombin, EPA was liberated from phospholipids and oxygenated (as judged by the formation of its monohydroxy derivative) whereas DHA was much less metabolized, although consistently transferred into PE.It is concluded that EPA and DHA might affect platelet aggregation via different mechanisms when pre-loaded in phospholipids. Whereas EPA is known to alter thromboxane A2 metabolism from endogenous arachidonic acid, by competing with it, DHA might act directly at the membrane level for inhibiting aggregation.

scholarly journals Cardiotonic effects of Terminalia arjuna extracts on guinea pig heart in vitro

2012 ◽  
Vol 7 (3) ◽  
Author(s):  
A.M. Mujibul Haq ◽  
Md. Mahbubul Huque ◽  
Shah Abdur Rahman Chaudhury ◽  
Mohammad Nurul Haque
Keyword(s):  
Guinea Pig ◽  
Terminalia Arjuna ◽  
Guinea Pig Heart

THE REDUCED CAPACITY OF THROMBOXANE FORMATION IN THROMBIN-PREACTIVATED PLATELETS IS NOT CAUSED BY DEPLETION OF THEIR ARACHIDONIC ACID POOL

1987 ◽  
Author(s):  
R E Scharf ◽  
M Stockschläder ◽  
H J Reimers ◽  
W Schneider
Keyword(s):  
Arachidonic Acid ◽  
Human Platelets ◽  
Thrombin Receptor ◽  
Precursor Pool ◽  
Acid Pool ◽  
Exogenous Arachidonic Acid ◽  
High Concentrations ◽  
Short Time ◽  
Thromboxane Formation

Thromboxane (TX) synthesis of washed human platelets pretreated with high concentrations of thrombin (0.5-2.0 U/ml) for 20 sec is significantly reduced upon further thrombin stimulation. Compared to controls (tyrode-pretreated platelets), thrombin-preactivated platelets recover normal TX synthesis following exposure to exogenous arachidonic acid (AA) indicating that short-time thrombin treatment does not inactivate platelet cyclooxygenase or TX synthetase (Blood 63: 858, 1984). To evaluate whether the reduced TX synthesis upon -the second thrombin exposure is due to depletion of their AA precursor pool, thrombin-pretreated platelets and tyrode-pretreated platelets (5×108/ml) were resuspended in autologous ACD plasma and incubated at 37°C with 0.2 μCi 14C-AA (20 μM) for 60 to 90 min in the presence of PGE1 (10 μM). Mean platelet uptake of 14C-AA (disappearance of radioactivity from the supernatant) was 12+3 nmoles AA/109 platelets and did not differ significantly between thrombin-pretreated platelets and controls. Thrombin-pretreated platelets released 10% or 4.5% of their 14c-activity upon further exposure to thrombin (2 U/ml) or collagen (8 μg/ml), respectively. The release from control platelets (15% with thrombin, 6.5% with collagen) did not differ from that of thrombin-pretreated platelets. However, even after incubation in ACD plasma, thrombin-pretreated platelets continued to form significantly less TXB2 (5.0±1.6 nmoles/109 platelets) than controls (9.7±2.2 nmoles/109 platelets, p< 0.05). These data indicate that the reduced capacity of thrombin-pretreated platelets is due neither to a depletion of the endogenous AA pool nor to an inactivation of cyclooxygenase or TX synthetase. The reduced TX synthesis capacity may be caused by a modification, destruction or desensitization of the platelet thrombin receptor as a consequence of the preceding thrombin stimulation.

Reduced glutathione modulates the arachidonic acid induced coronary reactions

1984 ◽  
Vol 62 (10) ◽  
pp. 1261-1267 ◽  
Author(s):  
Jaime Talesnik ◽  
James N. Tsoporis
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Reduced Glutathione ◽  
Isolated Heart ◽  
Prostaglandin E ◽  
Guinea Pig Heart ◽  
Rat Hearts ◽  
Resistance Vessels ◽  
Vasodilator Action ◽  
Perfused Hearts

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5–0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.

Inhibition Of Platelet Aggregation, Malonyldialdehyde And Thromboxane Formation By Hydroperoxides Of Arachidonic Acid

1981 ◽  
Author(s):  
D Aharonv ◽  
J B Smith ◽  
M J Silver
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Lipoxygenase Pathway ◽  
Dose Dependent Fashion ◽  
Induced Aggregation ◽  
Layer Chromatography ◽  
Dose Dependent ◽  
Thromboxane Formation

The arachidonate hydroperoxides 12-HPETE and 15-HPETE were biosynthesized from arachidonic acid using partially purified human platelet lipoxygenase or soybean lipoxidase respectively, and isolated by thin layer chromatography. Both compounds inhibited the arachidonic acid- induced aggregation of washed human platelets, suspended in calcium-free Krebs Henseleit solution, in a dose dependent fashion at concentrations between 1 and 50 uM. No inhibition was seen with up to 100 uM of these hydroperoxides when platelet -rich plasma was used. 12-HPETE (in micromolar concentrations) inhibited the formation of both thromboxane B2 (radioimmunoassay) and malonyldialdehyde (spectrophotometrie assay) when washed platelets were incubated with arachidonic acid. The 12-hydroxide, 12-HETE also inhibited platelet aggregation and thromboxane formation, but was less potent than 12-HPETE. We suggest that arachidonate hydroperoxide generated in platelets via the lipoxygenase pathway modulates platelet aggregation induced by arachidonic acid by inhibiting thromboxane formation.

Effect of ouabain on potassium exchange in hypothermic mammalian heart

1962 ◽  
Vol 203 (5) ◽  
pp. 834-838
Author(s):  
Sidney S. Schreiber ◽  
Murray Oratz ◽  
Marcus A. Rothschild
Keyword(s):  
Ventricular Fibrillation ◽  
Guinea Pig ◽  
Low Temperatures ◽  
Minimal Effect ◽  
Apparent Effect ◽  
Guinea Pig Heart ◽  
Cold Temperatures ◽  
Ouabain Inhibition ◽  
Potassium Exchange

Potassium exchange was studied in the intact working hypothermic guinea pig heart in vitro with K42. As at 37 C, buildup and washout experiments demonstrated two compartments of K exchange, but these behaved differently with reductions in temperature to 20 C. The rate of K exchange of the "fast" compartment decreased with lowered temperatures, whereas the rate of "slow" compartment exchange either remained unaffected or increased slightly. Ouabain had no apparent effect on the fast compartment K exchange. Toxic levels of ouabain, which inhibited entrance of K into the slowly exchanging phase at 37 C, showed a minimal effect on this compartment at 20 C. The decreased ouabain inhibition at 20 C was paralleled by a concomitant decrease in toxicity (contracture and ventricular fibrillation). It was postulated that intracellular cardiac K exchange involved two separate processes which responded differently to low temperatures. Ouabain action was indicated to be specifically on that process which was insensitive to cold temperatures.

Effect of Acetaldehyde on the Isolated, Non-working Guinea-Pig Heart: Independence of the Coronary Flow Increase from Changes in Heart Rate and Oxygen Consumption

1974 ◽  
Vol 52 (3) ◽  
pp. 602-612 ◽  
Author(s):  
Minh-Hau Nguyen ◽  
L. Gailis
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Guinea Pig ◽  
Gas Phase ◽  
Coronary Flow ◽  
Constant Pressure ◽  
Guinea Pig Heart ◽  
Bicarbonate Buffer

Guinea-pig hearts were perfused at constant pressure with Krehs–Henseleit bicarbonate buffer equilibrated with 95% O2 – 5% CO2. Acetaldehyde at 1 and 5 mM increased coronary flow, oxygen consumption, and heart rate. At 0.2 mM, it increased coronary flow and oxygen consumption only. In the rapidly paced heart, 1 mM acetaldehyde increased coronary flow, but not heart rate or oxygen consumption. Acetaldehyde increased coronary flow and oxygen consumption of the potassium-arrested heart. Acetaldehyde increased all parameters of the hypoxic heart (25% O2 gas phase), but the anoxic heart was not affected (coronary flow was already maximal).Reserpine (in vivo) and catecholamine β blockers (dichloroisoproterenol and propranolol) (in vitro) blocked the heart rate increases and moderated the rise in oxygen consumption. Dichloroisoproterenol plus phentolamine blocked the increases of both heart rate and oxygen consumption. None of the compounds affected the increase of coronary flow produced by acetaldehyde. Epinephrine, norepinephrine, and tyramine increased the heart rate and oxygen consumption, but not the coronary flow. Theophylline increased all three parameters. Neither tranylcypromine nor atropine modified the acetaldehyde effect. We conclude that the increase in heart rate is mediated by catecholamine β receptors. The increase in coronary flow is independent of the increase in heart rate or oxygen consumption and is not mediated by catecholamines.

Sign in / Sign up

Export Citation Format

Share Document