کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829183 | 1558991 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simvastatin evokes an unpredicted inhibition of β-adrenoceptor-mediated vasodilatation in porcine coronary artery
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
HMG-CoA reductase inhibitors, or statins, are widely used as cholesterol-lowering agents in the treatment of dyslipidemias. Statins have also been reported to have pleiotropic effects, independent of their effects on cholesterol synthesis, possibly through inhibition of the monomeric G proteins Ras and Rho, which are able to signal through ERK and Rho kinase activities, respectively. We have previously demonstrated that inhibition of ERK activation enhances β-adrenoceptor-mediated vasodilatation in the porcine isolated coronary artery. As statins can also inhibit ERK activation, the initial aim of this study was to determine whether statins have a similar influence on β-adrenoceptor-evoked vasodilatation. Segments of porcine distal coronary artery were mounted in a Mulvany wire myograph and bathed in Krebs-Henseleit buffer gassed with 95% O2/5% CO2 and maintained at 37 °C. Tissues were pre-contracted with the thromboxane mimetic U46619 prior to cumulative concentration-response curves to the β-adrenoceptor agonist salbutamol in the absence or presence of simvastatin (1, 5 or 10 μM), pravastatin (10 μM), or lovastatin (10 μM). Simvastatin inhibited the salbutamol-induced relaxation of the coronary artery. Similar effects were seen with lovastatin, but not pravastatin or the sodium salt of simvastatin. Simvastatin, but not pravastatin also inhibited the relaxations to the Ca2+-activated K+ channel opener NS1619 and the KATP channel opener pinacidil. Unexpectedly, these data indicate that, rather than enhancing β-adrenoceptor-mediated vasodilatation, lipophilic statins impair these responses. This is likely to be due to effects on K+ channels.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 690, Issues 1â3, 5 September 2012, Pages 158-163
Journal: European Journal of Pharmacology - Volume 690, Issues 1â3, 5 September 2012, Pages 158-163
نویسندگان
Chukwuemeka O. Uhiara, Stephen P.H. Alexander, Richard E. Roberts,