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Biomedical subjects

E Chabielska

Publications and source records attributed to E Chabielska.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phosphorothioate oligodeoxyribonucleotides antisense to PAI-1 mRNA increase fibrinolysis and modify experimental thrombosis in rats.

The effect of systemic inhibition of PAI-1 expression in rats by PS-16R, a phosphorothioate analogue of hexadecadeoxyribonucleotide complementary to a signal peptide coding sequence of rat PAI-1 mRNA, on PAI-1 activity in blood plasma and thrombus formation was studied in rat models for experimental thrombosis. In previous in vitro studies, oligonucleotides of PS-16R family have been shown to inhibit efficiently PAI-1 synthesis in endothelial cells by antisense mechanism. When PS-16R was administered intravenously as a single bolus injection (1 to 5 mg per rat), it produced a significant reduction in PAI-1 activity of blood plasma. This effect was both time- and concentration-dependent. Under the same conditions, three groups of rats were treated with control oligodeoxynucleotides such as PS-16R with double mismatches, with scrambled sequence, and an oligodeoxynucleotide with sense sequence (complementary to PS-16R), respectively. Based on these preliminary experiments, a low dose of 1.5 mg per rat was selected to produce approximately 20-30% reduction of PAI-1 activity in blood plasma and the effect of such a decrease in PAI-1 expression was tested on thrombus formation in two rat models for experimentally induced thrombosis. Such a limited decrease in PAI-1 activity produced a significant antithrombotic effect in the arterial thrombosis model. There was a profound delay in the occlusion time in rats treated with PS-16R when compared to control animals (80 +/- 3 and 55 +/- 3 h, respectively), although blood plasma activity of PAI-1 in the same groups of rats differed only by 20%. There was also a tendency to reduce both an incidence of venous thrombosis (58.33 and 68.11%, respectively) and thrombus weight (2.1 +/- 0.4 and 2.9 +/- 0.9 mg, respectively) in the animals treated with PS-16R. However, this effect was not significant. Thus, low dose of PS-16R through inhibition of PAI-1 synthesis in targeted cells in rats reduced PAI-1 activity in blood plasma and protected against arterial thrombus formation in the rat.

Animals↗
PubMed1998

Nitric oxide and prostacyclin are involved in antithrombotic action of captopril in venous thrombosis in rats.

The long-term administration of captopril to patients with a left ventricular dysfunction after myocardial infarction reduces the rate of recurrent coronary thrombosis. Thus, in the present study we investigated the influence of angiotensin-converting enzyme inhibitors (ACE-Is) on experimental venous thrombosis in normotensive rats and the involvement of NO and PGI2 in this effect. Animals were treated with captopril (1.5, 5 or 25 mg/kg twice daily, CAP), enalapril (15 mg/kg once daily, ENA) or distilled water for 10 days, per os. After ligation of the vena cava the thrombus weight decreased in both CAP and ENA treated rats. The effect was most pronounced in animals given the highest dose of CAP (p<0.0001 vs. control) and was significantly stronger than observed in ENA treated animals (CAP vs. ENA p<0.01). The mean blood pressure measured by the "tail cuff" method and platelet aggregation were not altered by either of the ACE-Is. The antithrombotic activity of CAP was reduced by indomethacin (2.5 mg/kg, s.c.) and independently by the NO-synthase inhibitor N(G)-nitro L-arginine methyl ester (3 mg/kg i.v. bolus + 3 mg/kg/h i.v. infusion, L-NAME). In the latter case CAP regained its antithrombotic properties in rats pretreated with L-Arginine (300 mg/kg i.v. + 300 mg/kg/h i.v.) before administration of L-NAME (p<0.05 vs. control). Moreover, the concomitant administration of indomethacin and L-NAME failed to completely abolish the antithrombotic action of captopril. Similar effects were observed in respect to the incidence of venous thrombosis. Our study documents a novel and important effect of ACE-Is on the vein thrombotic process and demonstrates the involvement of NO and PGI2 in this phenomenon.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

The antithrombotic effect of captopril and losartan on experimental arterial thrombosis in rats.

The mechanism by which ACE-Is (angiotensin converting enzyme inhibitors) reduces the rate of coronary thrombosis among patients with left ventricular dysfunction is not known. A potential interaction between the renin-angiotensin system (RAS) and the thrombotic process has been suggested. The goal of the present study was to evaluate the antithrombotic action of drugs which block the RAS by different mechanisms; captopril (50 mg/kg p.o.)-the angiotensin converting enzyme inhibitor and losartan (30 mg/kg p.o.)-the selective AT1 receptor antagonist. The normotensive rats were treated in acute or chronic manner (7 days) and then the arterial thrombosis was induced by insertion of a loop-shaped cannula into the abdominal aorta. The occlusion time (the period during which the loop was totally occluded by thrombus) was significantly prolonged in comparison with the control groups after chronic treatment with captopril (by 46%; p < 0.01) and losartan (by 42%; p < 0.05). Our results provide experimental evidence that the drugs blocking RAS exert an antithrombotic effect in the arterial thrombosis model in rats. This effect was independent from changes in blood pressure and primary hemostasis.

Angiotensin Receptor Antagonists↗
PubMed1996

The effect of tacrolimus (FK506) and cyclosporin A (CyA) on peripheral serotonergic mechanisms in uremic rats.

The aim of this study was to investigate the mechanism of hypertension and thromboembolic events induced by cyclosporin (CyA) and tacrolimus (FK506) in respect to their action on the serotonergic blood system. The study was carried out on healthy rats and those with experimental chronic renal failure. CyA injected into healthy and uremic rats caused an increase in serotonin (5-HT) concentration levels in whole blood and platelets. Concomitantly a rise in systolic blood pressure was observed. Platelet aggregation values were significantly higher in uremic rats given CyA. FK506 had no influence on 5-HT blood content, blood pressure or platelet aggregation values. It is concluded that 5-HT may play a role in the development of hypertension and thrombotic events caused by CyA. Furthermore, lower incidence of these complications during FK506 treatment could be the result of this drug's limited effect on the serotonergic blood system.

Animals↗
PubMed1996

Morphological and hemostatic changes in rats with abdominal arterial prosthesis.

We evaluated the changes over time in hemostatic factors during ongoing arterial thrombosis in rats, as induced by a loop-shaped aortic prosthesis. Moreover, we investigated this condition by inspecting in parallel local thrombus growth, systemic vascular prostacyclin and t-PA production. One minute after loop insertion, activated platelets spread on the internal surface of the prosthesis and 24 hrs later numerous platelet aggregates supported by a fibrin network could be observed. However, no evidence for platelet activation could be concomitantly found in peripheral blood. A sustained increased in PGI2 formation was detected together with a progressive increase in plasma fibrinolytic activity during thrombus growth. The levels of fibrinogen as well as antithrombin III (ATIII) and heparin cofactor II (HCII) activities were steadily increased in loop-bearing animals. In conclusion, the dynamic phases of thrombus formation, in an aortic prosthesis, produce changes in vascular function and in hemostatic factors at the level of systemic blood.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Losartan does not influence the blood platelet aggregation in normotensive rats.

Platelet aggregation was studied in PRP upon stimulation with ADP and collagen in normotensive rats treated with losartan (10 mg/kg). The acute and subchronic (5 days) losartan administration did not change the aggregating response of rat platelets. Similarly, in vitro study aggregation of platelets remained unaltered following incubation with losartan and its active metabolite EXP3174. In this study we presented the lack of influence of losartan and its main metabolite on rat platelet aggregation in normotensive rats.

Adenosine Diphosphate↗
PubMed1996

Influence of captopril on some haemostatic parameters in rats with ongoing process of venous thrombosis.

Recent laboratory findings strongly suggest that renin-angiotensin system plays an important role in regulation of haemostasis and fibrinolysis. In our previous study we showed that captopril exerts antithrombotic effect in venous thrombosis in rats. In this study we demonstrated that this effect is not a result of changes in platelet count, fibrinogen level alterations in blood coagulation pathways and fibrinolytic activity of the plasma. Further investigations are necessary to elucidate the mechanism of antithrombotic action of captopril.

Animals↗
PubMed1996

Effect of endothelin-1 on some hemostatic parameters in normotensive rats.

Some parameters of hemostasis and fibrinolysis were investigated in rats administered with endothelin-1 (ET-1). ET-1 (0.5, 1.0, 5.0 nmol/kg) dose-dependently shortened the bleeding time (BT). Concomitantly significant shortening of the clotting time (CT) was observed. ET-1 produced prolongation of the activated partial thromboplastin time (APTT), whereas prothrombin time (PT) remained unchanged. ET-1 did not influence in vitro platelet aggregation induced by ADP and collagen. The euglobulin clot lysis time (ECLT) was significantly shortened after ET-1 administration. Our results suggest that ET-1 modulates the process of hemostasis and fibrinolysis in the rat.

Animals↗
PubMed1993

Influence of Tołpa Peat Preparation on haemostasis in rats.

The influence of Tołpa Peat Preparation (TPP) on certain parameters of haemostasis was studied. The present results indicate that TPP (100, 200 and 300 mg/kg p.o.) had no influence on the bleeding time, clotting time, thrombin time, prothrombin time, kaolin-kephalin time, euglobulin lysis time, the concentration of fibrinogen, the platelet count and ADP-induced platelet aggregation. No changes in animals after long-term treatment with TPP (100 mg/kg for two weeks) were found either. In in vitro studies TPP given in concentrations 10(-5), 10(-4), 10(-3) and 10(-2) g/cm3 was used and certain changes of the studied parameters, probably caused by the presence of high salt content in this substance, were observed.

Amino Acids↗
PubMed1992

Influence of acetaldehyde on the vasopressor effect of serotonin in pithed rats.

In pithed rats, the intravenous (i.v.) administration of serotonin (3, 10, 30, 100, 300 and 1000 micrograms/kg) produced a dose-dependent increase in blood pressure. The pressor response to serotonin was reduced by acute acetaldehyde administration in a dose of 30 mg/kg i.v. and by 5-HT2 antagonist ketanserin (0.03 mg/kg i.v.). However, the lowest doses of acetaldehyde (10 and 20 mg/kg) were ineffective. In in vitro studies we also demonstrated that acetaldehyde (0.43 mM/l) and ketanserin (0.1 microM/l) inhibited the serotonin-induced vasoconstriction of isolated rat tail artery. In both experimental models the combination of acetaldehyde with ketanserin decreased the action of serotonin to the same extent as did ketanserin alone. In pithed rats pretreated with a high dose of ketanserin (3 mg/kg i.v.) serotonin produced hypotension by stimulation of 5-HT1 receptors. This effect was not enhanced by acetaldehyde (30 mg/kg) injection. Our data suggested that the action of acetaldehyde on the effects of serotonin in pithed rats was non-specific and independent of its interaction with serotonergic 5-HT1 and 5-HT2 receptors in blood vessels.

Acetaldehyde↗
PubMed1990

Influence of ethanol and serotonin on rat platelet aggregation.

We demonstrated that ethanol (1.0, 2.0 and 4.0 g/kg p.o.) significantly decreased blood platelet aggregation in a dose-dependent manner. The chronic administration of ethanol (6 g/kg daily for 4 weeks) also altered the sensitivity of rat platelets to ADP (4 mumol/l). We found that the acute and chronic administration of alcohol significantly increased the amplifying effect of 5-hydroxytryptamine (5-HT; 10(-6) mol/l) on ADP-induced aggregation. In all groups of rats, ketanserin (10(-5) mol/l) completely inhibited the amplification of aggregation induced by serotonin. In conclusion, the present results show that ethanol did not only produce inhibition of ADP-induced platelet aggregation but also affected the potentiating action of 5-HT on this process.

Administration, Oral↗
PubMed1990

Influence of acute and chronic ethanol administration on the vasopressor effect of serotonin in pithed rats.

In pithed rats, the intravenous administration of serotonin (3, 10, 30, 100, 300 and 1,000 micrograms/kg) produced a dose-dependent increase in blood pressure. This action of 5-HT was not changed by chronic ethanol intoxication (6.0 g/kg/day for 2 weeks). The pressor responses to serotonin were, in a dose-dependent manner, significantly reduced by acute ethanol administration (0.5, 1.0, 2.0 and 4.0 g/kg p.o.) and by ketanserin injection (0.03 mg/kg i.v.). However, ethanol (2.0 g/kg) did not amplify the dilator effect of serotonin in pithed rats pretreated with ketanserin (3.0 mg/kg i.v.). We also demonstrated that, in contrast to ketanserin (10(-7) mol/l), ethanol (0.05 mol/l) potentiated the serotonin-induced vasoconstriction of isolated rat tail arteries. These data suggest that the action of ethanol on the vasopressor effect of serotonin in pithed rats does not depend on its influence on serotonergic receptors in blood vessels.

Animals↗
PubMed1990

The serotonergic mechanisms are not involved in the inhibitory effect of captopril on rat platelet aggregation.

The influence of captopril on blood platelet aggregation and on serotonergic mechanisms in blood platelets were studied. In rats pretreated with captopril (10.0 mg/kg p.o.) platelet aggregation induced by ADP and collagen was significantly reduced. In vitro this drug had no inhibitory effect. Besides, captopril did not change the amplifying effect of serotonin on platelet aggregation. Captopril also had no influence on the uptake and storage of 5-hydroxytryptamine by rat blood platelets. These results show that serotonergic mechanisms are not involved in the suppressive effect of captopril on platelet aggregation.

Adenosine Diphosphate↗
PubMed1989

Cardiovascular effects of ethanol in anaesthetized, conscious and pithed rats.

The influence of ethanol (2.0 g/kg p.o.) on heart rate and blood pressure in anaesthetized, conscious and pithed rats was studied. In anaesthetized rats we observed an increase in heart rate and a marked and very sudden decrease in blood pressure. In pithed rats blood pressure decreased more slowly than in anaesthetized and conscious animals and there were no changes in heart rate. These results show that the central nervous system may be responsible for the increase in heart rate and early phase of hypotension caused by acute ethanol administration. The slower decrease (up to 1 h) in blood pressure may be caused by central and different indirect peripheral mechanisms.

Anesthesia↗
PubMed1989

[Effect of Polfos on the bleeding time. III. Changes in various parameters of the circulatory system].

The influence of Polfos on the blood pressure in rats was measured by direct and indirect methods. The influence of this pesticide on the heart rate was also examined. Two hours after Polfos administration an increase in blood pressure and a decrease in heart rate were observed. In the late phase of Polfos-intoxication no changes in the cardiovascular system were found. The results show that prolonged bleeding time in the initial phase of the intoxication might depend on its influence on the cardiovascular system in rats.

Animals↗
PubMed1989

[Effect of Polfos on the bleeding time. II. Changes in selected parameters of the blood coagulation system and fibrinolysis].

The influence of Polfos on some parameters of the coagulation system and fibrinolysis in rats was examined. The present results indicate that Polfos had no effect on the coagulation system and fibrinolysis in the initial phase of intoxication (2 hours). In the late phase of intoxication (24 hours) a decrease in the prothrombin index, shortening of thrombin time, increase in the fibrinogen level and prolongation of euglobulin lysis time were observed. The results demonstrate that the normalization of the bleeding time in the late phase of intoxication depended on activation of the coagulation system and inhibition of fibrinolysis activation.

Animals↗
PubMed1988

Effects of verapamil, diltiazem and nifedipine on some parameters of hemostasis in the rat.

Together with a mechanism such as activation of the coagulation system, vascular smooth muscle contraction and the activation of blood platelets are important processes in the hemostasis. Various calcium channel blockers besides those found to be vasodilators (1) have been shown to influence the functioning of blood platelets (2). They inhibit the aggregation induced by ADP, adrenaline, arachidonic acid or collagen (3). From these data it has been suggested that significant differences exist in the ability of calcium channel blockers to inhibit aggregatory responses (4). In order to elucidate further the possible role of calcium channel blockers in hemostasis we analyzed the effect of verapamil, diltiazem and nifedipine on the bleeding time, the amount of initial blood loss, platelet aggregation and some coagulation parameters in rats.

Animals↗