لا يتم عرض هذه النتيجة على الضيوف.
تسجيل الدخول للوصول الكامل.

لا يتم عرض هذه النتيجة على الضيوف.
تسجيل الدخول للوصول الكامل.

لا يتم عرض هذه النتيجة على الضيوف.
تسجيل الدخول للوصول الكامل.

لا يتم عرض هذه النتيجة على الضيوف.
تسجيل الدخول للوصول الكامل.

المؤلفون: Hirose, Masamichi, Takeishi, Yasuchika, Nakada, Tsutomu, Shimojo, Hisashi, Kashihara, Toshihide, Nishio, Ayako, Suzuki, Satoshi, Mende, Ulrike, Matsumoto, Kiyoshi, Matsushita, Naoko, Taira, Eiichi, Sato, Fumika, Yamada, Mitsuhiko

المصدر: PLoS ONE; Dec2012, Vol. 7 Issue 12, p1-13, 13p

مصطلحات موضوعية: NICORANDIL, HEART failure treatment, CARDIAC arrest, CORONARY disease, G proteins

مستخلص: Background: Beneficial effects of nicorandil on the treatment of hypertensive heart failure (HF) and ischemic heart disease have been suggested. However, whether nicorandil has inhibitory effects on HF and ventricular arrhythmias caused by the activation of G protein alpha q (Gαq) -coupled receptor (GPCR) signaling still remains unknown. We investigated these inhibitory effects of nicorandil in transgenic mice with transient cardiac expression of activated Gαq (Gαq-TG). Methodology/Principal Findings: Nicorandil (6 mg/kg/day) or vehicle was chronically administered to Gαq-TG from 8 to 32 weeks of age, and all experiments were performed in mice at the age of 32 weeks. Chronic nicorandil administration prevented the severe reduction of left ventricular fractional shortening and inhibited ventricular interstitial fibrosis in Gαq- TG. SUR-2B and SERCA2 gene expression was decreased in vehicle-treated Gαq-TG but not in nicorandil-treated Gαq-TG. eNOS gene expression was also increased in nicorandil-treated Gαq-TG compared with vehicle-treated Gαq-TG. Electrocardiogram demonstrated that premature ventricular contraction (PVC) was frequently (more than 20 beats/min) observed in 7 of 10 vehicle-treated Gαq-TG but in none of 10 nicorandil-treated Gαq-TG. The QT interval was significantly shorter in nicorandil-treated Gαq-TG than vehicle-treated Gαq-TG. Acute nicorandil administration shortened ventricular monophasic action potential duration and reduced the number of PVCs in Langendorff-perfused Gαq-TG mouse hearts. Moreover, HMR1098, a blocker of cardiac sarcolemmal KATP channels, significantly attenuated the shortening of MAP duration induced by nicorandil in the Gαq-TG heart. Conclusions/Significance: These findings suggest that nicorandil can prevent the development of HF and ventricular arrhythmia caused by the activation of GPCR signaling through the shortening of the QT interval, action potential duration, the normalization of SERCA2 gene expression. Nicorandil may also improve the impaired coronary circulation during HF. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)