NOVEL CARDIAC MYOFILAMENT DESENSITIZING SUBSTANCE RELEASED BY ENDOCARDIAL CELLS

心内膜细胞释放的新型心肌肌丝脱敏物质

• 批准号: 3767885
• 负责人: A SHAH
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3767885
• 关键词: calcium flux; endocardium; heart cell; heart contraction; laboratory rat; muscle cells; muscle relaxation; myofibrils; nitric oxide; papillary muscles; tissue /cell culture; vascular endothelium

Vascular endothelium regulates smooth muscle tone through the coordinated release of agents such as prostacycline, endothelium- derived relaxing factor (EDRF) or nitric oxide, and endothelin. Recent studies, both in isolated cardiac multicellular preparations and in intact hearts in vivo, indicated that endocardial endothelium may similarly influence myocardial contraction predominantly by modulating the onset of relaxation. Bioassay studies using cultured endocardial endothelial cells and isolated cardiac papillary muscle preparations suggest that diffusible agents are involved, one of which is probably nitric oxide. However, the relative contribution of endocardial endothelial and coronary vascular endothelial cells to these effects, and the myocardial mechanism of action of substances released by these cell types is unclear. We studied the effects of effluent of superfused endocardial and vascular endothelial cultured cells on contraction and intracellular calcium transients of isolated adult rat cardiac myocytes. Both endocardial and vascular endothelial cells tonically released a novel substance which rapidly and reversibly decreased the amplitude of myocytes twitch contraction by inducing earlier relaxation, and also increased diastolic cell length. These effects were not associated with any change in the intracellular calcium transient, indicating cardiac myofilament "desensitization". The activity of endothelial cell effluent remained stable at 37 degrees C for several hours or at 4 degrees C for at least 48 hours. The action of this substance did not involve nitric oxide, cyclic GMP or prostanoids, nor changes in intracellular pH. These properties suggest that endothelial cells may rapidly modulate cardiac contraction- relaxation coupling and diastolic tonus by altering myofilament properties, as well as exert distant effects because of the unusual stability of this substance

血管内皮通过膜调节平滑肌张力 药物如前列环素、内皮素、前列腺素、前列腺素等的协同释放。 衍生的舒张因子（EDRF）或一氧化氮和内皮素。 最近 研究，无论是在分离的心脏多细胞制剂， 完整的心脏在体内，表明内皮细胞可能 类似地，主要通过调节 放松的开始 使用培养的内皮细胞的生物测定研究 内皮细胞和分离的心脏乳头肌制备物 这表明，扩散剂参与，其中之一可能是 一氧化氮 然而，内分泌的相对贡献 内皮细胞和冠状血管内皮细胞对这些作用的反应， 以及这些释放的物质的心肌作用机制 细胞类型不清楚。 我们研究了污水的影响 灌流内皮细胞和血管内皮细胞培养细胞， 离体成年大鼠心肌收缩和细胞内钙瞬变 心肌细胞 内皮细胞和血管内皮细胞 紧张性地释放一种新的物质， 通过诱导心肌细胞的收缩幅度降低 舒张早期，舒张期细胞长度也增加。 这些 影响与细胞内的任何变化无关。 钙瞬变，表明心肌肌丝“脱敏”。 内皮细胞流出液的活性在37 ℃时保持稳定 在4摄氏度下保持至少48小时。 的 这种物质的作用不涉及一氧化氮，环GMP或 前列腺素，也没有细胞内pH值的变化。这些特性表明， 内皮细胞可以快速调节心脏收缩 通过改变肌丝的松弛偶联和舒张张力 属性，以及发挥遥远的影响，因为不寻常的 这种物质的稳定性