Aging and Endothelial Function of Muscle Arterioles

肌肉小动脉的衰老和内皮功能

• 批准号: 6509968
• 负责人: JUDY M DELP
• 金额: $ 21.28万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6509968
• 关键词: aging; animal old age; arterioles; enzyme inhibitors; exercise; gastrocnemius muscle; gene expression; laboratory rat; mature animal; messenger RNA; microcirculation; musculoskeletal circulation; nitric oxide; nitric oxide synthase; polymerase chain reaction; prostaglandin endoperoxide synthase; prostaglandins; striated muscles; tissue /cell preparation; vascular endothelium; vascular resistance; vasodilation; vasodilators

DESCRIPTION: (Verbatim from application) Skeletal muscle perfusion and endothelium-mediated vasodilation of the skeletal muscle resistance vasculature appear to diminish with advancing age; however, the precise mechanisms that underlie aging-induced decrements in vasodilatory function of the skeletal muscle vasculature are unclear. Our recent work has documented impaired flow-induced vasodilation in 1A arterioles from soleus and gastrocnemius muscles of aged Fischer 344 rats. Although flow-induced vasodilation of skeletal muscle arterioles is known to be an endothelium-dependent response, the mechanisms of the response have not been defined in arterioles from locomotory muscles, such as the soleus and gastrocnemius muscles, and furthermore, the mechanisms which underlie the aging-induced impairment of this response are not known. Therefore, we propose to investigate the contribution of endothelium-dependent vasodilatory pathways to flow-induced vasodilation in soleus and gastronemius muscle arterioles from young and aged Fisher 344 rats. We will test the hypothesis that the aging-induced impairment of flow-induced vasodilation in these resistance arterioles occurs primarily due to a decrease in the ability of the endothelium to produce prostanoid vasodilators. We will use specific inhibitors of key enzymes to determine which component(s) of the flow-induced vasodilation, i.e., endothelial nitric oxide (NO), prostanoid vasodilators, or endothelium-derived hyperpolarizing factor (EDEHF), is downregulated in arterioles from old animals (Aim 1). We will determine whether decreases in protein and mRNA expression for the constitutive form of cyclooxygenase (COX-1) and endothelial nitric synthase (ecNOS) potentially underlie reduced production of No and prostanoid vasodilators in response to flow in arterioles from old rats (Aim2). Finally, because an increased tendency toward more sedentary behavior occurs with advancing age and because exercise training has been shown to improve endothelium-dependent vasodilation of the skeletal muscle vasculature, we propose to determine whether exercise training can ameliorate the impaired flow-induced vasodilation that occurs in skeletal muscle arterioles from aged rats (Aim 3). Although aging has been documented to reduce skeletal muscle vasodilatory responses, these studies will be the first to evaluate the endothelial mechanisms responsible for the loss of vasodilatory function. Furthermore, these studies will determine whether exercise training can counter the aging-associated loss of endothelium-dependent vasodilatory responses in skeletal muscle resistance arterioles.

描述：（应用程序的逐字）骨骼肌灌注和 内皮介导的骨骼肌抵抗血管的血管舒张 随着年龄的增长，似乎会减少；但是，确切的机制 基础衰老引起的骨骼血管舒张功能的降低 肌肉脉管系统尚不清楚。我们最近的工作记录了障碍 比目鱼和胃癌的1a小动脉中流动诱导的血管舒张 老年菲舍尔344只大鼠的肌肉。尽管流动引起的血管舒张 骨骼肌小动脉被称为内皮依赖性反应， 响应的机制尚未在小动脉中定义 机车肌肉，例如比目鱼和腹骨肌，以及 此外，衰老引起的损害的机制 响应尚不清楚。因此，我们建议调查贡献 内皮依赖性的血管舒张途径的流动性血管舒张 来自年轻和老年人的344只大鼠的比目鱼和胃肠肌动脉。 我们将测试以下假设 这些电阻小动脉中的血管舒张主要是由于减少 在内皮产生前列腺类血管扩张剂的能力中。我们将 使用密钥酶的特定抑制剂来确定哪些成分的成分 流动诱导的血管舒张，即内皮一氧化氮（NO），前列腺素 血管扩张剂或内皮衍生的超极化因子（EDEHF）为 在老动物的小动脉中下调（AIM 1）。我们将确定是否 蛋白质和mRNA表达的降低 环氧合酶（COX-1）和内皮氮合酶（ECNOS）可能有可能 响应 来自老鼠的小动脉流动（AIM2）。最后，因为趋势增加了 朝着更久坐的行为迈进，随着年龄的增长和锻炼而发生 已显示训练可改善内皮依赖性血管舒张 骨骼肌脉管系统，我们建议确定运动训练是否 可以改善骨骼中流量引起的血管舒张受损 来自老鼠的肌肉动脉（AIM 3）。尽管已经记录了老化 减少骨骼肌血管舒张反应，这些研究将是第一项 评估负血管舒张损失的内皮机制 功能。此外，这些研究将决定运动训练是否 可以应对与内皮相关的衰老相关的依赖性血管舒张的损失 骨骼肌抗性小动脉的反应。

项目成果

Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles.

衰老会损害大鼠骨骼肌小动脉的内皮依赖性血管舒张功能。

• DOI: 10.1152/ajpheart.00004.2002
• 发表时间: 2002
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Muller-Delp,JudyM;Spier,ScottA;Ramsey,MichaelW;Delp,MichaelD
• 通讯作者: Delp,MichaelD

Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide.

运动训练增强老年大鼠骨骼肌阻力动脉中血流诱导的血管舒张：PGI2 和一氧化氮的作用。

• DOI: 10.1152/ajpheart.00588.2006
• 发表时间: 2007
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Spier,ScottA;Delp,MichaelD;Stallone,JohnN;Dominguez2nd,JamesM;Muller-Delp,JudyM
• 通讯作者: Muller-Delp,JudyM