Maturation and myogenic reactivity of cerebral arteries

脑动脉的成熟和肌源反应性

• 批准号: 6688269
• 负责人: JOHN N BUCHHOLZ
• 金额: $ 20.5万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688269
• 关键词: age difference; angiogenesis; apical membrane; blood pressure; brain circulation; calcium flux; cerebral artery; electrophysiology; guanylate cyclase; intracellular; laboratory mouse; membrane potentials; muscle tone; myogenesis; newborn animals; nitric oxide; potassium channel; ryanodine; sarcoplasmic reticulum; tetraethylammonium compound; thapsigargin; vascular smooth muscle; vasoconstriction; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): We have shown that maturation increases the magnitude and sensitivity of myogenic reactivity in neonatal cerebral arteries compared to adult mice. Myogenic constriction first appears at 10 mm Hg in cerebral arteries from neonatal mice (5 d) compared to 40 mm Hg in cerebral arteries from adult mice (6-8 wk). Myogenic tone was maintained throughout each step increase in pressure in cerebral arteries from adult mice. In arteries from neonatal nice, myogenic tone was significantly greater at each pressure step compared to response in arteries from adult mice. Wall thickness was similar between groups. In a separate series of experiments, the contractile effect of tetraethylammonium (TEA; a KCa channel blocker) was determined in cerebral arteries from neonatal and adult mice. TEA caused adult and neonatal arteries to constrict; however, constriction in arteries from adult mice was significantly greater compared to arteries from neonatal mice suggesting that KCa channel activity is less in the neonate. Combined, our data suggest that arteries from neonatal mice possess the mechanisms necessary to constrict to increases in pressure. Furthermore, cerebral arteries from neonatal mice develop myogenic tone at lower pressures and to a greater extent compared to arteries from adult mice. Finally, vascular smooth muscle KCa channels modulate myogenic tone in arteries from neonatal mice to a lesser extent compared to arteries from adult mice. These findings have led to the general hypothesis that: maturation decreases the sensitivity and extends the range of pressure-induced myogenic tone of mouse cerebral blood vessels. In order to determine the effects of maturation on myogenic reactivity, pressure, microfluorometry, and electrophysiological experiments will be conducted in arteries taken from newborn (3-5 day) and adult mice (6-8 wk). To determine the relative importance of smooth muscle mechanisms, diameter, intracellular Ca++ and membrane potential experiments will be conducted in endothelium-denuded middle cerebral artery segments. These experiments will enable an unparalleled assessment of the mechanisms whereby maturation affects myogenic reactivity.

描述（由申请人提供）：我们已经证明成熟度会增加 新生儿大脑肌源性反应的强度和敏感性 与成年小鼠的动脉相比。肌源性收缩首先出现在 10 毫米处 新生小鼠脑动脉中的汞（5 天）与小鼠脑动脉中的 40 毫米汞柱相比 来自成年小鼠的脑动脉（6-8周）。肌源性张力得以维持 在每一步中，成年小鼠的脑动脉压力都会增加。 在新生儿的动脉中，肌源性张力在每个 压力阶跃与成年小鼠动脉反应的比较。壁厚 组间相似。在一系列单独的实验中， 四乙铵（TEA；一种 KCa 通道阻滞剂）的收缩作用 在新生和成年小鼠的脑动脉中测定。 TEA 引起成人 和新生儿动脉收缩；然而，动脉收缩 成年小鼠的动脉明显大于新生小鼠的动脉 表明新生儿 KCa 通道活性较低。综合起来，我们的数据 表明新生小鼠的动脉具有必要的机制 收缩以增加压力。此外，脑动脉来自 新生小鼠在较低压力下更大程度地产生肌原性张力 与成年小鼠的动脉相比。最后，血管平滑肌KCa 通道将新生小鼠的动脉肌源性张力调节至较小 与成年小鼠的动脉相比。这些发现导致 一般假设：成熟会降低敏感性并延长 压力引起的小鼠脑血管肌源性张力的范围。在 为了确定成熟对生肌反应性、压力、 显微荧光测定法和电生理学实验将在 取自新生小鼠（3-5 天）和成年小鼠（6-8 周）的动脉。确定 平滑肌机制、直径、细胞内 Ca++ 的相对重要性 膜电位实验将在内皮细胞裸露的情况下进行 大脑中动脉段。这些实验将实现无与伦比的 评估成熟影响肌原反应性的机制。