Exercise and Vascular Function in Paraplegic

截瘫患者的运动和血管功能

• 批准号: 6759393
• 负责人: STEPHEN E DICARLO
• 金额: $ 51.95万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759393
• 关键词: adrenergic receptor; exercise; laboratory rat; messenger RNA; neuropeptide Y; nitric oxide synthase; paraplegia; polymerase chain reaction; superoxide dismutase; sympathetic nervous system; ultrasound blood flow measurement; vascular endothelium; vasoconstriction

DESCRIPTION (provided by applicant): Individuals with spinal cord injuries (SCl) above T6 experience episodic bouts of life-threatening hypertension termed autonomic dysreflexia (AD). If not treated promptly, the hypertension may produce cerebral and sub-arachnoid hemorrhage, seizures, ventricular arrhythmias, renal failure, and may lead to death. Enhanced vasoconstrictor responses to sympathetic stimulation may account for some, if not the majority, of the pressor response of AD. Sympathetic stimulation causes vasoconstriction by co-releasing norepinephrine onto alpha-adrenergic receptors, neuropeptide Y (NPY) onto Y1 receptors and ATP onto P2x purinoreceptors. To date, only the role of alpha-adrenergic receptor hyper-responsiveness in mediating AD has been investigated. This is surprising since it is well documented that the pattern of sympathetic nerve activity determines the relative contribution that each co-transmitter makes to vasoconstriction. Importantly, SCI alters the pattern of sympathetic activity. Furthermore, the influence of SCI on endothelium-dependent vasodilation and buffering of sympathetically mediated vasoconstriction has not been investigated. Importantly, endothelial derived nitric oxide and vasodilatory prostacyclin buffers the vasoconstrictor response to sympathetic stimulation. Finally, measures designed to reduce vasoconstrictor hyper-responsiveness have not been examined. A single bout of dynamic exercise attenuates the post-exercise vasoconstrictor response to sympathetic stimulation. Thus, the ability of vessels to respond to a change in sympathetic nerve activity after exercise is attenuated. Therefore, this proposal is designed to assess the role of sympathetic co-transmitters, endothelial function, and molecular adaptations on vasoconstrictor responses in intact and paraplegic rats. In addition, the effects of a single bout of exercise on vasoconstrictor responses will be examined. The clinical significance of the post-exercise modulation of vascular function will be determined by the evaluating the cardiovascular and sympathetic nerve responses to colon distension.

描述（由申请人提供）：T6上方的脊髓损伤（SCL）的个体经历了威胁生命的高血压的情节性，称为自主性肌反应症（AD）。如果未迅速治疗，高血压可能会导致脑和蛛网膜下腔出血，癫痫发作，心室心律失常，肾衰竭，并可能导致死亡。增强的血管收缩反应对交感神经刺激的反应可能是AD的压力响应的某些（即使不是大多数）。交感神经刺激通过将去甲肾上腺素共同释放到α-肾上腺素能受体，神经肽Y（NPY）上引起血管收缩，并在Y1受体上，然后将ATP与P2X Purinoreceptors上。迄今为止，仅研究了α-肾上腺素能受体超反应在介导AD中的作用。这是令人惊讶的，因为有充分的文献证明，交感神经活动的模式决定了每个共晶剂对血管收缩的相对贡献。重要的是，科幻改变了交感神经活动的模式。此外，尚未研究SCI对交感神经介导的血管收缩的内皮依赖性血管舒张和缓冲的影响。重要的是，内皮衍生的一氧化氮和血管舒张前列环蛋白缓冲血管收缩对交感神经刺激的反应。最后，尚未检查旨在降低血管收缩超反应性的措施。一次动态运动会减轻运动后血管收缩对交感神经刺激的反应。因此，锻炼后血管对交感神经活动变化的反应能力减弱。因此，该提案旨在评估同性恋副传播者，内皮功能以及对完整和截瘫大鼠血管收缩反应的分子适应性的作用。此外，将检查一次运动对血管收缩反应的影响。运动后调节血管功能的临床意义将通过评估心血管和交感神经对结肠延伸的反应来确定。