Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery

Froldi, Guglielmina; Bertin, Riccardo; Dorigo, P.; Montopoli, Monica; Caparrotta, Laura

doi:10.1111/j.2042-7158.2011.01313.x

Cited by 14 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Use of elinogrel, a novel reversible P2Y12 antagonist, did not affect vasoconstriction stimulated by α,β-metATP and was associated with less bleeding (19). Similar results were obtained when the impact of clopidogrel on a rat caudal artery was researched (20). Even though, this pro-drug requires hepatic activation, thus having no ADP-antagonist activity in vitro, it caused relaxation of arterial tissues and had an impact on vascular smooth muscle cell proliferation.…”

Section: Impact On Endothelium and Vascular Tonesupporting

confidence: 61%

See 1 more Smart Citation

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Adamski¹,

Koziński²,

Ostrowska³

et al. 2014

Thromb Haemost

View full text Add to dashboard Cite

SummaryDual antiplatelet therapy consisting of one of the P2Y12 receptor inhibitors in conjunction with aspirin is the mainstay of treatment for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary interventions (PCI). In recent years, multiple extra-platelet features of P2Y12 receptor antagonists have been reported in numerous clinical trials. The aim of this review is to summarise reported pleiotropic effects of clopidogrel, prasugrel, ticagrelor and other P2Y12 receptor blockers. We included observations made both in human and in animal models, together with proposed mechanisms of action for described features. If confirmed in randomised studies and properly applied to everyday practice, the observed extraplatelet actions could enable us to improve efficacy of ACS and post-PCI treatment, as well as to confine mortality and occurrence rate of cardiovascular events.

show abstract

Section: Impact On Endothelium and Vascular Tonesupporting

confidence: 61%

“…Inflammatory processes, endothelial function, vascular tone, adenosine plasma levels and cardioprotection were reported to be affected by P2Y12 blockers (12,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). These off-target actions can be beneficial, but might also be associated with adverse side effects.…”

Section: Introductionmentioning

confidence: 99%

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Adamski¹,

Koziński²,

Ostrowska³

et al. 2014

Thromb Haemost

View full text Add to dashboard Cite

show abstract

“…Similarly, clopidogrel caused relaxation of arterial tissues and influenced VSMC proliferation directly without hepatic biotransformation in vitro . The effect was independent of endothelium, β‐adrenoceptor and purinergic P2 receptors (Froldi et al, ).…”

Section: Effects On Vascular Functionmentioning

confidence: 99%

Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

Nylander

Schulz

2016

British J Pharmacology

View full text Add to dashboard Cite

The effect and clinical benefit of P2Y 12 receptor antagonists may not be limited to platelet inhibition and the prevention of arterial thrombus formation. Potential additional effects include reduction of the pro-inflammatory role of activated platelets and effects related to P2Y 12 receptor inhibition on other cells apart from platelets. P2Y 12 receptor antagonists, thienopyridines and ticagrelor, differ in their mode of action being prodrugs instead of direct acting and irreversibly instead of reversibly binding to P2Y 12 . These key differences may provide different potential when it comes to additional effects. In addition to P2Y 12 receptor blockade, ticagrelor is unique in having the only well-documented additional target of inhibition, the equilibrative nucleoside transporter 1. The current review will address the effects of P2Y 12 receptor antagonists beyond platelets and the protection against arterial thrombosis. The discussion will include the potential for thienopyridines and ticagrelor to mediate anti-inflammatory effects, to conserve vascular function, to affect atherosclerosis, to provide cardioprotection and to induce dyspnea. Abbreviations

show abstract

“…[22] Clopidogrel has been reported to exhibit vasomodulatory activity [23] and direct endothelial effects independent from antiplatelet actions, [24] which are still not fully understood. Recently, Froldi et al [25] reported that the clopidogrel pretreatment of rats resulted in only a slight decrement of the constriction response of the aortic tissues to phenylephrine in vitro. In the present study, ) concentration in the clopidogrel group was observed to be reduced in comparison with the response in the control group, there was no significant difference in the responses between the two groups for increased ACh concentrations.…”

Section: Discussionmentioning

confidence: 99%

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

Özkısacık¹,

Discigil²,

Kurtoğlu³

et al. 2012

Turk Gogus Kalp Dama

View full text Add to dashboard Cite

Amaç: Bu çalışmada, asetilsalisilik asit (ASA), klopidogrel ve tirofiban gibi antitrombositer ajanların sıçan torasik aort segmentinde asetilkolin (ACh) ile uyarılan gevşeme yanıt-ları üzerine olan etkileri araştırıldı. Ça lış ma pla nı: Yirmi sekiz adet ağırlıkları 250-300 g arasında olan Wistar-albino türü yetişkin erkek sıçan çalışmaya alındı. Sıçanlar randomize olarak dört gruba ayrıldı: ASA grubu (n=7), klopidogrel grubu (n=7), tirofiban grubu (n=7) ve kontrol grubu (n=7). Deneyden 12 saat önce intraperitoneal (İP) ASA (1.5 mg/kg) veya klopidogrel (1 mg/kg) enjeksiyonları yapıldı. Tirofiban grubunda, 150 μgr/kg tirofiban İP deneyden 1 ve 12 saat önce olmak üzere, iki kez verildi. Kontrol grubundaki sıçanlara herhangi bir ilaç verilmedi. Sıçanlar dekapite edildikten sonra torasik aort segmentleri çıkartıldı ve oksijenize Krebs çözeltisi içinde organ banyosuna asıldı ve aort halkalarında asetilkolin ile uyarılan gevşeme yanıtının doza bağımlı değişimleri incelendi. Bul gu lar: Asetilkolinin en düşük molar konsantrasyonu (10-9) ile elde edilen gevşeme yanıtının ASA (%94.3±3.3) ve klopidogrel (%94.6±3.1) grubunda kontrol (%86.7±8.1) grubuna göre azalmış olduğu bulundu (p<0.05). Daha yük-sek asetilkolin konsantrasyonlarında ise, tüm gruplarda gevşeme yanıtlarının benzer olduğu gözlemlendi. So nuç: Asetilsalisilik asit ve klopidogrel tedavilerinin sonucunda endotel aracılı gevşeme yanıtında hafif bir gecikme ortaya çıkmış ve tirofibanın belirgin bir etkisi olmamıştır. Bu bulgular ASA ve klopidogrelin endotel aracılı vazodilatasyon üzerinde sınırlı bir etkisi olabileceğini düşündürmektedir.Anah tar söz cük ler: Asetilsalisilik asit; klopidogrel; endotel; tirofiban. Background:In this article, we aimed to investigate the effects of antithrombotic agents, including acetyl salicylic acid (ASA), clopidogrel, and tirofiban on the acetylcholine (ACh)-induced dilation responses in rat thoracic aorta segments. Methods: Twenty-eight Wistar albino male rats weighing between 250-300 g were included in the study. The rats were randomly divided into four groups: the ASA group (n=7), the clopidogrel group (n=7), the tirofiban group (n=7), and the control group (n=7). Intraperitoneal (IP) injection of ASA (1.5 mg/kg) or clopidogrel (1 mg/kg) was administered 12 hours before the experiment. In the tirofiban group, 150 μgr/kg tirofiban IP was given twice at one and 12 hours before the experiment. The rats in the control group did not receive any medication. After the rats were decapitated, the segments of the thoracic aorta were removed and suspended in an oxygenated Krebs solution in a tissue bath, and the dose dependency in the responses to the ACh-induced dilation in the aortic rings were studied. Results:The dilation responses of the aortic rings to ACh in the lowest molar concentration (10-9) were found to be reduced in the ASA (94.3%±3.3) and clopidogrel (94.6%±3.1) groups when compared with the control group (86.7%±8.1) (p<0.05). The responses to higher concentrations of ACh were observed to be similar in all of the groups....

show abstract

Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery

Cited by 14 publications

References 36 publications

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

Contact Info

Product

Resources

About

Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery

Cited by 14 publications

References 36 publications

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Effects of P2Y12 receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

Contact Info

Product

Resources

About

Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines