01 January 2001
Studies on the antithrombotic action of AT1 receptor antagonists.
Władysław Buczko, Tomasz Matys, Robert Pawlak, Iwona Kucharewicz, Ewa ChabielskaMed Sci Monit 2001; 7(4): BR600-605 :: ID: 421097
Abstract
Background: In our previous experiments we showed that the prototype memberof the AT1 receptor antagonists (AT1-As) family, losartan, prevented the development of arterial andvenous thrombosis in rats. Recent studies have demonstrated that apart from blocking AT1 receptor, losartanis also a competitive antagonist to thromboxane A2/prostaglandin H[sub]2[/sub] receptor (TP receptor). Thus, wedecided to assess if this feature could contribute to the antithrombotic action of losartan.
Material and methods: We compared the influence losartan, its active metabolite EXP3174 and valsartan on rat plateletadhesion to fibrillar collagen and platelet aggregation in response to thromboxane A2 analogue, U46619.We also assessed the efficacy of these drugs in platelet-dependent pulmonary thrombosis in mice as wellas preventive and therapeutic models of venous thrombosis in rats.
Results: All the three compounds,given in a single dose, inhibited rat platelet adhesion to fibrillar collagen and platelet aggregationinduced with U46619 in vitro and ex vivo, with the action of losartan being much more pronounced thanthat of EXP3174 or valsartan. Losartan also more effectively protected mice from death in response tothe intravenous injection of collagen / epinephrine and it was the only compound which reduced mice mortalityafter the intravenous injection of U46619. In contrast, all the three AT1 receptor antagonists exerteda similar thrombolytic action and comparably decreased the thrombus weight in the therapeutic and preventivemodel of venous thrombosis, although in the latter case a high dose of losartan was slightly more effectivethan a corresponding dose of EXP3174 and valsartan.
Conclusions: Since losartan is endowed with a relativelylow affinity towards the AT1 receptor, we conclude that its superiority over EXP 3174 and valsartan ininhibiting thrombocyte function and platelet-dependent thrombosis could result from its stronger actionon the TP receptor. This feature seems to be less important in the thrombolytic effect of AT1-As andin the inhibition of the venous thrombosis development, in which platelets play only a minor role.
Keywords: AT1 receptor antagonists, Platelet, Thrombosis
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952