[Show abstract][Hide abstract] ABSTRACT: For decades nitrites (NO2−) and nitrates (NO3−) were thought to be the stable end products of nitric oxide (NO) produced by NO synthases (NOS). However, it is evident now that, nitrite is reduced back to bioactive NO along an oxygen and physiological pH gradient by a variety of mechanisms, including enzymatic reduction by deoxyhemoglobin or xanthine oxidoreductase (XOR).
Recently, it was demonstrated that nitrite induced vasodilation in hypertensive rats is mediated by XOR-dependent reduction of nitrite to nitric oxide (NO) . The aim of this study was to analyze the role of XOX in anti-platelet and antithrombotic activities of nitrite in rats with renovascular hypertension, induced by partial ligation on the left renal artery. Arterial thrombosis was induced electrically in carotid artery and nitrite effects on thrombus weight, ex vivo platelet activity, fibrynolysis and coagulation parameters, as well as nitrosylhemoglobin (NOHb) and nitrite/nitrate plasma concentration were assessed in presence and absence of XOX inhibitors. Sodium nitrite (NaNO2) was administered twice a day for 3 days (p.o.) in a dose of 0.17 mmol/kg, and allopurinol (ALLO) and febuxostate (FEB) (p.o.) in doses of 100 mg/kg and 5 mg/kg, respectively, 30 minutes before nitrite administration (n = 13–19). Nitrite decreased thrombus weight (TW) (0.48 ± 0.03 mg vs VEH 0.88 ± 0.08 mg; p < 0.001), but FEB only partially reversed this effect (TW = 0.63 ± 0.06 mg; p < 0.05 vs nitrites), while ALLO was without the effect (TW = 0.43 ± 0.02 mg). On the other hand, in nitrite-treated animals, collagen (5 µg/ml)-induced whole blood platelet aggregation ex vivo (70.5 ± 7.1% vs VEH 100 ± 4.5%; p < 0.05) as well as stirring -induced TXB2 release were substantially reduced while FEB and ALLO fully reversed these effects. NOHb, nitrite/nitrate concentration in plasma increased profoundly in nitrite-treated rats to micromolar range of concentrations. In in vitro assay antiplatelet effects of nitrite (10–1000 µM) was fully reversed by FEB not only in normoxic but also in hypoxic conditions. In addition, nitrite treatment decreased PAI-1 concentration (0.47 ± 0.13 ng/ml vs VEH 0.62 ± 0.04 ng/ml; p < 0.05) and FEB or ALLO reversed this effect (0.66 ± 0.52 ng/ml and 0.69 ± 0.05 ng/ml). In contrast, PT, APTT, TT, fibrinogen level, QUICK, t-PA level, α2-antiplasmin activity remained unchanged after nitrite treatment. Interestingly, fibrinogen generation was blunted in nitrite-treated animals and neither FEB nor ALLO reversed this effect. In summary, nitrite reduction to NO by XOR, but not by deoxyhemoglobin, plays a major role in antiplatelet effect of nitrite in vivo in rats. However, the antithrombotic effect of nitrite also involves XOR-independent mechanisms of NO generation affecting coagulation.
[Show abstract][Hide abstract] ABSTRACT: Coffee may exert a preventive effect on arterial thrombosis. Trigonelline is one of the most abundant compounds in coffee that undergoes pyrolysis upon roasting of coffee beans. The aim of the present study was to identify pyridinium compounds formed upon trigonelline pyrolysis and coffee roasting and to investigate the effect of three of them, i.e., 1-methylpyridine and 1,3- and 1,4-dimethylpyridine, on experimentally induced arterial thrombosis in rats. 1,3- and 1,4-dimethylpyridine but not 1-methylpyridine inhibited arterial thrombus formation. 1,3-Dimethylpyridine inhibited platelet aggregation and reduced fibrin formation in platelet-rich plasma, whereas 1,4-dimethylpyridine increased the plasma level of 6-keto-PGF1α. 1,4-Dimethylpyridine slightly increased rat tissue plasminogen activator plasma activity. In summary, we demonstrated that pyridinium compounds display mild antithrombotic properties due to stimulation by prostacyclin release (1,4-dimethylpyridine) and inhibition of platelet aggregation (1,3-dimethylpyridine). Those pyridinium compounds may, to some extent, be responsible for the beneficial effects of coffee drinking.
Journal of Agricultural and Food Chemistry 03/2014; 62(13). DOI:10.1021/jf5008538 · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ACE2 alternatively converts angiotensin (Ang) II into Ang-(1-7) and Ang I into Ang-(1-9). There is little information in the literature with respect to Ang-(1-9) properties. A number of studies show a link between peptides of the renin-angiotensin system and thrombosis.
We have investigated the influence of Ang-(1-9) on stasis-induced venous thrombosis in the rat. The contribution of coagulation and fibrinolytic systems, angiotensin receptor type 1 (AT1) and MAS receptor in the mode of Ang-(1-9) action was also determined.
Ang-(1-9) enhanced thrombosis development, decreased plasma concentration of tissue plasminogen activator and increased the level of its inhibitor (PAI-1). The action of Ang-(1-9) was reversed by selective antagonist of AT1 receptor, but not Ang-(1-7) antagonist. Ang-(1-9) did not bind to the AT1 receptor.
Ang-(1-9) enhances venous thrombosis in the rat because of the impairment of fibrinolysis. The prothrombotic effect of Ang-(1-9) is mediated by Ang II acting via the AT1 receptor.
Journal of Renin-Angiotensin-Aldosterone System 07/2013; 15(1). DOI:10.1177/1470320313498631 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A substantial amount of evidence links the renin-angiotensin system with thrombosis. For example, ACE inhibitors and angiotensin receptor blockers possess independent of the hemodynamic changes, antithrombotic activity. Aliskiren direct renin inhibitor belongs to a new very promising antihypertensive drug that effectively inhibits the renin-angiotensin system. The aim of study was to determine the influence of aliskiren on stasis-induced venous thrombosis in renovascular hypertensive and normotensive rats. The involvement of nitric oxide and prostacyclin in the potential antithrombotic action was also elucidated. Six weeks after clipping of the left renal artery rats developed hypertension which was confirmed by the "tail cuff" method. Hypertensive and normotensive rats were treated with aliskiren (10, 30 and 100mg/kg/day) per os for 10days. Venous thrombosis was induced by stasis of vena cava inferior. Aliskiren at the highest dose induced a significant decrease in systolic blood pressure in hypertensive, but did not change this parameter in normotensive rats. Oral administration of aliskiren resulted in dose-dependent decrease of venous thrombus weight in hypertensive and normotensive rats. The antithrombotic activity of aliskiren was abolished both by NO synthase inhibitor and prostacyclin synthesis inhibitor. Aliskiren decreased collagen-induced platelet aggregation, increased plasma level of tissue plasminogen activator activity whereas no changes in plasminogen activator inhibitor activity and coagulation parameters were found. We showed that aliskiren prevents the development of venous thrombosis by enhanced fibrinolysis and the blood platelet inhibition via nitric oxide and/or prostacyclin-dependent mechanism.
Thrombosis Research 11/2012; 131(1). DOI:10.1016/j.thromres.2012.11.001 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared the antithrombotic effects in vivo of 2 chemically different carbon monoxide-releasing molecules (CORM-A1 and CORM-3) on arterial and venous thrombus formation and on hemostatic parameters such as platelet activation, coagulation, and fibrinolysis. The hypotensive response to CORMs and their effects on whole blood gas analysis and blood cell count were also examined.
CORM-A1 (10-30 µmol/kg, i.v.), in a dose-dependent fashion, significantly decreased weight of electrically induced thrombus in rats, whereas CORM-3 inhibited thrombosis only at the highest dose used (30 µmol/kg). CORM-A1 showed a direct and stronger inhibition of platelet aggregation than CORM-3 in healthy rats, both in vitro and in vivo. The antiaggregatory effect of CORM-A1, but not CORM-3, correlated positively with weight of the thrombus. Concentration of active plasminogen activator inhibitor-1 in plasma also decreased in response to CORM-A1, but not to CORM-3. Neither CORM-A1 nor CORM-3 had an effect on plasma concentration of active tissue plasminogen activator. CORM-3, but not CORM-A1, decreased the concentration of fibrinogen, fibrin generation, and prolonged prothrombin time. Similarly, laser-induced venous thrombosis observed intravitally via confocal system in green fluorescent protein mice was significantly decreased by CORMs. Although both CORM-A1 and CORM-3 (30 µmol/kg) decreased platelets accumulation in thrombus, only CORM-A1 (3-30 µmol/kg) inhibited platelet activation to phosphatidylserine on their surface.
CORM-3 and CORM-A1 inhibited thrombosis in vivo, however CORM-A1, which slowly releases carbon monoxide, and displayed a relatively weak hypotensive effect had a more pronounced antithrombotic effect associated with a stronger inhibition of platelet aggregation associated with a decrease in active plasminogen activator inhibitor-1 concentration. In contrast, the fast CO releaser CORM-3 that displayed a more pronounced hypotensive effect inhibited thrombosis primarily through a decrease in fibrin generation, but had no direct influence on platelet aggregation and fibrynolysis.
[Show abstract][Hide abstract] ABSTRACT: Heparin is a natural polymer widely used in medicine especially during the treatment of cardiovascular diseases since it is a potent blood anticoagulant. In case of emergency, e.g., massive hemorrhage, the anticoagulant activity of heparin has to be quickly stopped by the administration of a heparin reversing agent. Currently protamine sulfate, an allergenic protein, is used for this purpose. We are reporting the studies on a new polymeric substance, a cationic dextran derivative, which is able to form complexes with heparin. Dextran is a blood compatible polymer which is also frequently applied in medicine. By substituting dextran with glycidyltrimethylammonium chloride a cationic polymer was obtained that in vitro binds to heparin with an efficiency similar to that of protamine. To investigate the influence of modified dextran on the reversal of conventional heparin we used the models of experimental arterial thrombosis induced by electrical stimulation and chemically induced venous thrombosis. A decrease in bleeding time and activated partial thromboplastin time after administration of the cationic dextran to heparinized rats was found. Moreover, other routinely measured blood parameters are significantly affected. Modified dextran, in contrast to protamine sulfate, significantly increases red blood cell counts, hemoglobin level, and hematocrit value. The data we obtained show that the modified dextran may reduce anticoagulative heparin activity both under in vivo and in vitro conditions. Further clinical studies are needed to estimate whether modified dextran could replace protamine sulfate, especially in dialyzed patients with the end-stage renal disease associated with anemia.
European journal of pharmacology 05/2012; 686(1-3):81-9. DOI:10.1016/j.ejphar.2012.04.037 · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Periodontal disease is mainly associated with the activity of bacteria which adhere to the tooth surface and form specific structure of bacterial biofilm. Periodontal bacteria cause inflammation of the gums and aggressive immune response, affecting the periodontium. The first phase of initial therapy - mechanical removal of dental plaque and calculus - is necessary. If this non-surgical therapy has proved to be unsuccessful, an alternative treatment with antimicrobial agents is then considered. Pharmacotherapy is based on systemic or local antibiotics and/or antiseptics, which are applied according to the severity of the disease. A number of recent periodontal studies present some of the pharmacological agents, that are directed against bacteria or a host immune response, are often chosen as an adjunct treatment option, but none of these antimicrobials were established as 'a gold standard' in the periodontal treatment. This review provides some present recommendation of pharmacological strategies, with particular emphasis on systemic and local antimicrobial therapy of periodontal disease.
Advances in Medical Sciences 11/2011; 56(2):123-31. DOI:10.2478/v10039-011-0044-9 · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Angiotensin (Ang) (1-9) is the renin-angiotensin-system peptide found in the plasma of healthy volunteers and after angiotensin-converting-enzyme inhibitors therapy. In vitro experiments proved that Ang-(1-9) may be produced from Ang I. In our study, we tried to expand the poor data about the in vivo properties of Ang-(1-9). We revealed that Ang-(1-9) enhanced electrically stimulated arterial thrombosis in the carotid artery of Wistar rats. Losartan, a selective blocker of AT1 receptor for Ang II, abolished the prothrombotic activity of Ang-(1-9). This peptide increased plasma level of fibrinogen, augments fibrin generation, and similarly to Ang II, potentiated collagen induced platelet aggregation. Using HPLC, we found that after incubation of Ang-(1-9) with platelet homogenates or after intravenous administration this peptide is converted to Ang II. We concluded that Ang-(1-9) exerts an Ang II-like prothrombotic effect due to the conversion to Ang II in the circulatory system of rats and that platelets are involved in this process.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 06/2010; 61(3):317-24. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence has accumulated that point to the tissue plasminogen activator (tPA), a serine protease historically associated with blood physiology, as an important regulator of the central nervous system functioning. tPA is highly expressed in the limbic system where it regulates neuronal viability and experience-induced plasticity. In the amygdala tPA is a critical mediator of stress-induced structural and functional rearrangements that ultimately shape up behavioral responses to stressful stimuli. The importance of tPA in the limbic system was confirmed using tPA-deficient mice; these animals do not show biochemical, structural and behavioral signatures normally associated with stress. tPA-mediated facilitation of experience-induced plasticity in the limbic system is mediated by a complex mechanism that may involve direct or indirect interactions of tPA with NMDA receptor, its binding to the LRP receptor or activation of brain-derived growth factor.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 8:135-46. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that topically applied nicotinamide and its metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of dermatological disorders such as acne vulgaris and rosacea.
This study aimed to find out if the mechanism of these therapeutic effects depends on their vascular effects, by investigating if nicotinamide and NMN(+) are able to influence vascular permeability of the vessels in the skin on the back of Wistar rats.
A dose-dependent increase in vascular permeability was seen in rats treated intradermally with nicotinamide and NMN(+). Interestingly, a significantly stronger effect of NMN(+) compared with nicotinamide was evident. Increased vascular permeability in rats treated with 0.5% NMN(+) ointment was seen. Moreover, indomethacin, a cyclo-oxygenase 1 and 2 inhibitor and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, reduced the observed effects of nicotinamide and NMN(+).
This study provides direct in vivo evidence that nicotinamide and its metabolite NMN(+) increase skin vascular permeability in rats by a mechanism that may involve NO and prostaglandins.
[Show abstract][Hide abstract] ABSTRACT: So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma.
Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6). Control groups were saline-sensitized challenged with OVA (VEH/OVA, n = 6) and OVA-sensitized challenged with saline (OVA/VEH, n = 6). Plasmin system components were determined in the plasma by ELISA. Plasminogen activator inhibitor-1 (PAI-1) was localized by an immunohistochemical reaction.
Sensitization and challenge with OVA caused thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions. Serum total IgE was significantly higher in OVA-sensitized rats as compared to VEH-sensitized control groups. Tissue plasminogen activator activity was significantly decreased in asthmatic animals (4.48 +/- 0.4 vs. 6.7 +/- 0.3 ng/ml for OVA/OVA and OVA/VEH; p < 0.05), and PAI-1 activity was statistically significantly higher in asthma rats (0.8 +/- 0.05 vs. 0.5 +/- 0.03 ng/ml for OVA/OVA vs. OVA/VEH; p < 0.05). alpha2-Antiplasmin was higher in rats receiving OVA sensitization than in those that were sham sensitized (p < 0.05). Immunohistochemical staining for PAI-1in the lungs of asthmatic animals showed very strong PAI-1 expression in lung inflammatory cells.
We have demonstrated for the first time the existence of PAI-1 in lung inflammatory cells of rats with asthma. This finding was consistent with the superiority of plasmin system inhibition over activation in plasma.
International Archives of Allergy and Immunology 08/2008; 147(3):190-6. DOI:10.1159/000142041 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN). To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA) sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC). In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01). In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.
[Show abstract][Hide abstract] ABSTRACT: 1-methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti-thrombotic activity of MNA in vivo.
Antithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis).
MNA (3-100 mg kg(-1)) induced a dose-dependent and sustained thrombolytic response, associated with a rise in 6-keto-PGF(1alpha) in blood. Various compounds structurally related to MNA were either inactive or weaker thrombolytics. Rofecoxib (0.01-1 mg kg(-1)), dose-dependently inhibited the thrombolytic response of MNA, indomethacin (5 mg kg(-1)) abolished it, while L-NAME (5 mg kg(-1)) were without effect. MNA (3-30 mg kg(-1)) also reduced arterial thrombosis and this effect was abrogated by indomethacin (2.5 mg kg(-1)) as well as by rofecoxib (1 mg kg(-1)). MNA, however, did not affect venous thrombosis. In vitro MNA did not modify platelet aggregation nor induce vasodilation.
MNA displayed a profile of anti-thrombotic activity in vivo that surpasses that of closely related compounds. MNA inhibited platelet-dependent thrombosis by a mechanism involving cyclooxygenase-2 and prostacyclin. Our findings suggest that endogenous MNA, produced in the liver by nicotinamide N-methyltransferase, could be an endogenous activator of prostacyclin production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system.
British Journal of Pharmacology 10/2007; 152(2):230-9. DOI:10.1038/sj.bjp.0707383 · 4.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are few findings indicating that nicotinamide may potentially influence intravascular thrombosis. Interestingly, N-methylnicotinamide, one of the metabolites of nicotinamide - could be more potent than its parent compound. In the present study we have investigated the influence of N-methylnicotinamide on arterial thrombosis in normotensive and renovascular hypertensive rats. The contribution of platelets, coagulation and fibrinolytic systems in the mode of N-methylnicotinamide action was also determined. Furthermore, we examined the role of nitric oxide/prostacyclin in the mechanisms of N-methylnicotinamide action. N-methylnicotinamide, but not nicotinamide, administered intravenously into renovascular hypertensive rats developing electrically induced arterial thrombosis caused dose-dependent decrease of thrombus weight, collagen-induced platelet aggregation and plasma antigen/activity of plasminogen activator inhibitor - 1, without changing of occlusion time, routine coagulation parameters and plasma activity of tissue plasminogen activator. Indomethacin - an inhibitor of prostacyclin synthesis, completely abolished the antithrombotic and antiplatelet effect of N-methylnicotinamide, and the plasma level of 6-keto-PGF(1alpha) , prostacyclin metabolite, increased simultaneously with the inhibition of thrombus formation. Our study shows that N-methylnicotinamide via production/release of prostacyclin inhibits arterial thrombosis development. The antithrombotic effect of N-methylnicotinamide is accompanied by platelet inhibition and enhanced fibrinolysis, due to the decrease production of plasminogen activator inhibitor - 1.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 10/2007; 58(3):515-27. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats. In the arterial thrombosis model, a bolus injection of SAK-RGD-K2-Hir was less effective than rt-PA and r-SAK. However, the most effective in the improvement and maintenance of carotid patency and in arterial thrombus mass reduction was SAK-RGD-K2. In contrast, all r-SAK derivatives reduced venous thrombus weight significantly in comparison to r-SAK and r-Hir. However, the most observable decrease in thrombus weight was obtained after application of recombinant proteins containing the r-Hir. The bleeding time was significantly prolonged in the animals treated with proteins containing r-Hir at a dose of 1.0 mg/kg. There were no observable changes in plasma fibrinogen concentration. In conclusion, our findings show thrombolytic activity in intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hir in rats. Although this protein compares favourably with r-SAK in rat venous thrombolysis, we were unable to confirm the beneficial effects of SAK-RGD-K2-Hir over r-SAK and rt-PA in the carotid artery thrombolysis model. Furthermore, our results also suggest that SAK-RGD-K2-Hir bears a risk of bleeding, but this may be true for higher doses.
Thrombosis and Haemostasis 07/2007; 97(6):1037-45. DOI:10.1160/TH06-10-0562 · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the use of angiotensin converting enzyme inhibitors (ACE-Is) in clinical practice brought the great chance to recognize the RAS role in the physiology and pathology, there are still many questions which we cannot answer. This article reviews actually known pathways of angiotensin II (Ang II) and other peptides of renin-angiotensin system (RAS) production and their physiological significance. The various carboxy- and aminopeptidases generate a range of peptides, like Ang II, Ang III, Ang IV, Ang-(1-7) and Ang-(1-9) possessing their own and known biological activity. In this issue especially the alternative pathways of Ang II synthesis involving enzymes other than angiotensin-converting enzyme (ACE) are discussed. We present many evidences for the significance of a new pathway of Ang II production. It has been clearly shown that Ang I may be converted to Ang-(1-9) by angiotensin-converting enzyme-related carboxypeptidase (ACE-2) and then into Ang II in some tissues, but the enzymes responsible for this process are unknown till now. Although there are many data proving the existence of alternative pathways of Ang II production, we can still block only ACE and angiotensin receptor 1 (AT(1)) in clinical practice. It seems that a lot needs to be done before we can wildly complexively control RAS and treat more effectively cardiovascular disorders such as hypertension or heart failure.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2007; 57(4):529-39. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study compared the antithrombotic effect of plasma angiotensin converting enzyme inhibitors (ACE-Is): captopril (CAP), enalapril (ENA) and tissue ACE-Is: perindopril (PER), quinapril (QUIN) in experimental venous and arterial thrombosis. Normotensive Wistar rats were treated p.o. with CAP (75 mg/kg), ENA (20 mg/kg), PER (2 mg/kg) and QUIN (3 mg/kg) for 10 days. The influence of ACE-Is on coagulation and fibrinolytic systems as well as platelet function was evaluated. The hypotensive effect of ACE-Is was equal in all groups. QUIN maintained the final carotid blood flow at the highest value in comparison to PER and plasma ACE-Is. The arterial thrombus weight was reduced in PER and QUIN groups while venous thrombus weight was also reduced after CAP. Tissue and plasma ACE-Is caused the inhibition of platelet adhesion and aggregation. A reduction of fibrin generation, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and shortening of euglobulin clot lysis time (ECLT) were observed after PER and QUIN treatment. In conclusion, given in equipotent hypotensive doses, tissue ACE-Is exerted more pronounced antithrombotic effect than plasma ACE-Is in experimental thrombosis. The differences between tissue and plasma ACE-Is in terms of their more pronounced inhibition of experimental thrombosis may be related to the intensified activation of fibrinolysis and inhibition of coagulation.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 07/2006; 57(2):231-45. · 2.72 Impact Factor