کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473185 | 1550385 | 2018 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Beta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca2+ handling dysfunction in rats with pulmonary artery hypertension
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کلمات کلیدی
SCWWCESarco(endo)plasmic reticulumLTCCPLNmonocrotalineMCTPAHBeta-blocker - بتا بلوکرright ventricle - بطن راستCa2+ handling - دست زدن به Ca2 +phospholamban - فسفولامبنPulmonary arterial hypertension - فشار خون شریانی ریویBeta blocker - مسدود کننده بتاCardiac myocyte - میوسیت قلبیRight heart failure - نقص قلب راستpulmonary artery hypertension - پرفشاری خون عروق ریویL-type Ca2+ channel - کانال Ca2 + L نوع
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Right heart failure is the major cause of death in Pulmonary Artery Hypertension (PAH) patients but is not a current, specific therapeutic target. Pre-clinical studies have shown that adrenoceptor blockade can improve cardiac function but the mechanisms of action within right ventricular (RV) myocytes are unknown. We tested whether the β1-adrenoceptor blocker metoprolol could improve RV myocyte function in an animal model of PAH, by attenuating adverse excitation-contraction coupling remodeling. PAH with RV failure was induced in rats by monocrotaline injection. When PAH was established, animals were given 10â¯mg/kg/day metoprolol (MCTâ¯+â¯BB) or vehicle (MCT). The median time to the onset of heart failure signs was delayed from 23â¯days (MCT), to 31â¯days (MCTâ¯+â¯BB). At 23â¯Â±â¯1â¯days post-injection, MCTâ¯+â¯BB showed improved in vivo cardiac function, measured by echocardiography. RV hypertrophy was reduced despite persistent elevated afterload. RV myocyte contractility during field stimulation was improved at higher pacing frequencies in MCTâ¯+â¯BB. Preserved t-tubule structure, more uniform evoked Ca2+ release, increased SERCA2a expression and faster ventricular repolarization (measured in vivo by telemetry) may account for the improved contractile function. Sarcoplasmic reticulum Ca2+ overload was prevented in MCTâ¯+â¯BB myocytes resulting in fewer spontaneous Ca2+ waves, with a lower pro-arrhythmic potential. Our novel finding of attenuation of defects in excitation contraction coupling by β1-adrenoceptor blockade with delays in the onset of HF, identifies the RV as a promising therapeutic target in PAH. Moreover, our data suggest existing therapies for left ventricular failure may also be beneficial in PAH induced RV failure.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 120, July 2018, Pages 74-83
Journal: Journal of Molecular and Cellular Cardiology - Volume 120, July 2018, Pages 74-83
نویسندگان
Ewan D. Fowler, Mark J. Drinkhill, Ruth Norman, Eleftheria Pervolaraki, Rachel Stones, Emma Steer, David Benoist, Derek S. Steele, Sarah C. Calaghan, Ed White,