کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3028851 1183030 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation into the mechanism(s) of antithrombotic effects of carbon monoxide releasing molecule-3 (CORM-3)
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Investigation into the mechanism(s) of antithrombotic effects of carbon monoxide releasing molecule-3 (CORM-3)
چکیده انگلیسی

Carbon monoxide (CO) like nitric oxide (NO) has been recognized as activator of soluble guanylate cyclase (sGC) in many physiological functions. Studies, which demonstrate the mechanisms by which CO inhibits platelet aggregation in in vivo models, are few. Here we investigated the possible involvement of sGC, NO, plasminogen activator inhibitor (PAI-1) and p38 MAP Kinase in antithrombotic effects of CO released by a novel, water-soluble, CO releasing molecule-3 (CORM-3) using rat. The effects of CORM-3 on in vitro and ex vivo platelet aggregation induced by thrombin as well as in in vivo thrombosis models were studied. When added to rat washed platelets in in vitro study, CORM-3 (100 and 200 μM) inhibited thrombin-induced platelet aggregation. Similarly, antiplatelet effect was also observed when 3 mg/kg i.v. infusion of CORM-3 administered for 10 minutes in ex vivo study using rat. Interestingly, in presence of inhibitor of sGC (ODQ, 10 mg/kg, i.p.) and inhibitor of nitric oxide synthase (L-NAME, 30 mg/kg, i.p.), inhibition of thrombin-induced aggregation by CORM-3 was significantly blocked. Notably, in presence of inhibitor of KATP channel (glibenclamide, 10 mg/kg, i.p.) and p38 MAP Kinase (SCIO-469, 1 mg/kg, i.p.), inhibition of aggregation by CORM-3 was not blocked. In in vivo studies using animal models of thrombosis, we found that CORM-3-mediated antithrombotic effect was dependent on activation of sGC, NO and suppression of PAI-1 in arterial thrombosis and Arterio-Venous (A-V) shunt models. Therefore, we concluded that antithrombotic activity of CORM-3 may be mediated by activation of sGC, NO and inhibition of PAI-1.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 127, Issue 6, June 2011, Pages 551–559
نویسندگان
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