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：（来自应用程序的逐字记录）骨骼肌灌注和 内皮介导的骨骼肌阻力血管舒张 似乎随着年龄的增长而减少;然而， 衰老引起的骨骼肌血管舒张功能减退的基础 肌肉脉管系统尚不清楚。我们最近的研究表明 比目鱼肌和腓肠肌1A小动脉血流诱导的血管舒张 老年Fischer 344大鼠的肌肉。虽然血流诱导的血管舒张 已知骨骼肌小动脉是内皮依赖性反应， 反应的机制尚未在小动脉中确定， 运动肌肉，如比目鱼肌和腓肠肌，以及 此外，衰老引起的这种损伤的机制 回应尚不清楚。因此，我们建议调查 内皮依赖性血管舒张途径对血流诱导的血管舒张的影响 比目鱼肌和腓肠肌小动脉。 我们将检验这一假设： 这些阻力小动脉的血管舒张主要是由于 内皮细胞产生前列腺素类血管扩张剂的能力。我们将 使用关键酶的特异性抑制剂来确定 流动诱导的血管舒张，即，内皮型一氧化氮（NO），前列腺素类 血管扩张剂，或内皮源性超极化因子（EDEHF）， 在来自老年动物的小动脉中下调（Aim 1）。我们将决定 蛋白质和mRNA表达的组成型的减少， 环氧合酶（考克斯-1）和内皮型一氧化氮合酶（ecNOS）可能 导致NO和前列腺素类血管扩张剂的产生减少， 来自老年大鼠的小动脉中的流量（Aim 2）。最后，因为越来越多的人 随着年龄的增长，人们会倾向于久坐不动的行为， 训练已经显示出改善血管的内皮依赖性血管舒张， 骨骼肌血管，我们建议确定是否运动训练 可以改善骨骼肌中发生的受损的血流诱导的血管舒张， 老年大鼠肌小动脉（Aim 3）。尽管衰老已经被记录下来， 减少骨骼肌血管舒张反应，这些研究将是第一个 评估血管舒张功能丧失的内皮机制， 功能此外，这些研究将确定运动训练是否 可以对抗衰老相关的内皮依赖性血管舒张功能的丧失， 骨骼肌阻力小动脉的反应。

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