کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9013022 | 1125052 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition](/preview/png/9013022.png)
چکیده انگلیسی
The vasorelaxation activities of MCPT, a newly synthesized xanthine derivative, were investigated in this study. In phenylephrine (PE)-precontracted rat aortic rings with intact endothelium, MCPT caused a concentration-dependent relaxation, which was inhibited by endothelium removed. This relaxation was also reduced by the presence of nitric oxide synthase inhibitor LÏ-nitro-L-arginine methylester (L-NAME, 100 μM), soluble guanylyl cyclase (sGC) inhibitors methylene blue (10 μM), 1 H-[1,2,4] oxidazolol [4,3-a] quinoxalin-1-one (ODQ, 1 μM), adenylyl cyclase (AC) blocker SQ 22536 (100 μM), ATP-sensitive K+ channel blocker (KATP) glibenclamide (1 μM), a Ca2+ activated K+ channels blocker tetraethylammonium (TEA, 10 mM) and a voltage-dependent potassium channels blocker 4-aminopyridine (4-AP, 100 μM). The vasorelaxant effects of MCPT together with IBMX (0.5 μM) had an additive action. In PE-preconstricted endothelium-denuded aortic rings, the vasorelaxant effects of MCPT were attenuated by pretreatments with glibenclamide (1 μM), SQ 22536 (100 μM) or ODQ (1 μM), respectively. MCPT enhanced cAMP-dependent vasodilator isoprenaline- and NO donor/cGMP-dependent vasodilator sodium nitroprusside-induced relaxation activities in endothelium-denuded aortic rings. In A-10 cell and washed human platelets, MCPT induced a concentration-dependent increase in intracellular cyclic GMP and cyclic AMP levels. In phosphodiesterase assay, MCPT displayed inhibition effects on PDE 3, PDE 4 and PDE 5. The inhibition % were 52 ± 3.9, 32 ± 2.6 and 8 ± 1.1 respectively. The Western blot analysis on HUVEC indicated that MCPT increased the expression of eNOS. It is concluded that the vasorelaxation by MCPT may be mediated by the inhibition of phosphodiesterase, stimulation of NO/sGC/ cGMP and AC/cAMP pathways, and the opening of K+ channels.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 76, Issue 8, 7 January 2005, Pages 931-944
Journal: Life Sciences - Volume 76, Issue 8, 7 January 2005, Pages 931-944
نویسندگان
Yi-Ching Lo, Huei-Hsia Tsou, Rong-Jyh Lin, Deng-Chyang Wu, Bin-Nan Wu, Young-Tso Lin, Ing-Jun Chen,