Alterations of the functions of imidazoline-1 and alpha 2 adrenergic receptors in the medulla oblongata in the development of heart failure

延髓中咪唑啉 1 和 α 2 肾上腺素能受体在心力衰竭发展过程中功能的改变

• 批准号: 12670702
• 负责人: SATO Naoki
• 金额: $ 2.05万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670702/
• 关键词: Heart Failure; Imidazoline receptor; alpha2 adrenergic receptor; α_2アドレナリン受容体; 交換神経系; 心機能; 圧受容体反射

Background/Goal : Sympathetic activation is a hallmark of heart failure (HF). Clinical investigation have demonstrated usefulness of beta-blocker treatment for HF. However, it has not been well established whether nor not central symapthoinhibition could be favorable for the progression of HF, although it is known that activation of imidazoline receptors in central nervous system suppresses sympathetic outflow and decreases plasma norepinephrine levels. Therefore, our goal was to examine the effects of chronic administration of an imidazoline receptor agonist, rilmenidine (RIL), on HF in conscious beagles.Methods : Twelve beagles were chronically instrumented for intra-atrial infusions of saline or RIL (0.5mg/kg/day over 5 weeks) and rapid pacing at 250 bpm. Echocardiography was performed before and after HF for measurements of left ventricular ejection fraction (LVEF), % fractional shortening (%FS), and LF end-diastolic dimension (EDD).Results : Heart rate, %FS, LVEF, and EDD between control (C, n=6) and RIL(n=6) groups were not different before HF (C:126±31,38.1±9.0,68.1±11.0,35.6±3.5, RIL:121±17bpm,39.7±6.6%,70.8±7.9%,33.4±4.1mm, respectively). LV functions (%FS, LVEF, and EDD) in RIL group was significantly (p<0.05) better than C (15.3±6.9 vs 7.7±2.4%,32.5±12.5 vs 17.2±5.2%,4.5±5.0 vs 48.0±2.0 mm, respectively).Conclusion : Central sympathoinhibition tolerated the development of HF, suggesting chronic suppression of symapthetiv outflow might be useful for the treatment of HF.

背景/目的：交感神经激活是心力衰竭（HF）的标志。临床研究已证明β受体阻滞剂治疗HF的有效性。然而，尽管已知中枢神经系统中咪唑啉受体的激活抑制交感神经流出并降低血浆去甲肾上腺素水平，但中枢交感神经抑制是否有利于HF的进展还没有很好地确定。因此，我们的目标是研究慢性管理的咪唑啉受体激动剂，利美尼定（RIL），对HF清醒beagles.Methods的影响：12只比格犬长期instrumented为心房内注入生理盐水或RIL（0.5mg/kg/天，超过5周）和快速起搏250 bpm。结果：对照组（n=6）和RIL组（n=6）在HF前的心率、%FS、LVEF和EDD均无显著性差异（C组：126± 31，38.1 ± 9.0，68.1 ± 11.0，35.6 ±3.5; RIL组：121± 17 bpm，39.7 ± 6.6%，70.8 ± 7.9%，33.4 ±4.1mm）。LV函数RIL组的%FS、LVEF和EDD显著高于对照组（P <0.05），（p<0.05）优于C（15.3±6.9 vs 7.7± 2.4%，32.5 ±12.5 vs 17.2± 5.2%，4.5 ±5.0 vs 48.0±2.0 mm）。中枢交感神经抑制耐受HF的发展，表明慢性抑制交感神经流出可能有助于HF的治疗。

项目成果

Effects of central sympathoinhibition via imidazoline receptor activation on the progression of heart failure in conscious beagles

通过咪唑啉受体激活抑制中枢交感神经对清醒比格犬心力衰竭进展的影响

• 发表时间: 2003
• 期刊: Circ J 67
• 作者: Tokuyama K;Sato N;et al.
• 通讯作者: et al.

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》

• 发表时间: 2006
• 期刊: Seibutsu Butsuri 46(1)
• 作者: Yasushi Shigeri;Keiko Shimamoto
• 通讯作者: Keiko Shimamoto