Mechanisms of 5-hydroxytryptamine-induced hypotension

5-羟色胺诱发低血压的机制

基本信息

  • 批准号:
    8018166
  • 负责人:
  • 金额:
    $ 3.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-01-21 至 2013-07-20
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Hypertension is a sustained elevation in blood pressure that represents a significant risk factor for common causes of morbidity and mortality including, heart disease, stroke, and end-stage renal disease. Despite research efforts, the exact mechanism underlying essential hypertension remains largely unknown, interestingly, several lines of evidence suggest an important association between hypertension and serotonin (5-hydroxytryptamine, 5-HT). Studies have demonstrated elevated levels of free plasma 5-HT in Doth human and animal models of hypertension compared to normotensive controls. Historically, these elevated levels were thought to contribute to essential hypertension. However, we have shown that elevated free plasma 5-HT has the ability to lower blood pressure in male deoxycorticosterone acetate (DOCA)-salt hypertensive and sham-normotensive rat. The mechanism underlying 5-HT-induced hypotension is not yet mown. We hypothesize that elevated levels of free plasma 5-HT lower blood pressure in a nitric oxide dependent manner by reducing total peripheral resistance. This may be the result of either a reduction in sympathetic nervous system (SNS) tone and/or stimulation of a vascular 5-HT receptor(s). An integrative approach will be used to elucidate the mechanism underlying 5-HT-induced hypotension. We will use several different techniques, including whole animal measures, SNS activity measures, and measures of vascular reactivity. The aims for this study are as follows: Specific aim 1: will test the hypothesis that 5-HT-induced hypotension is mediated by a fall in total peripheral resistance in the DOCA-salt and sham rat. Specific aim 2: will test the hypothesis that chronic 5-HT infusion reduces sympathetic nerve activity or stimulates sensory afferent nerves. Specific aim 3: will test the hypothesis that 5-HT stimulates vascular receptors, leading to a release of nitric oxide, and vascular relaxation. This research will fill a gap in our understanding of how 5-HT functions in the cardiovascular system and explore the potentially beneficial role of 5-HT in hypertension. Additionally, this project may lead to discovery of novel therapeutic targets for the treatment of essential hypertension.
描述(由申请人提供):高血压是血压持续升高,是导致心脏病、中风和终末期肾病等常见发病和死亡原因的重要危险因素。尽管进行了研究努力,原发性高血压的确切机制仍然很大程度上未知,有趣的是,一些证据表明高血压和血清素(5-羟色胺,5-HT)之间存在重要关联。研究表明,与正常血压对照相比,Doth 人类和动物高血压模型中游离血浆 5-HT 水平升高。从历史上看,这些升高的水平被认为会导致原发性高血压。然而,我们已经证明,升高的游离血浆 5-HT 能够降低雄性醋酸去氧皮质酮 (DOCA)-盐高血压和假血压正常大鼠的血压。 5-HT 引起的低血压的机制尚未阐明。我们假设游离血浆 5-HT 水平升高,通过降低总外周阻力,以一氧化氮依赖性方式降低血压。这可能是交感神经系统 (SNS) 张力降低和/或血管 5-HT 受体刺激的结果。将采用综合方法来阐明 5-HT 诱发低血压的机制。我们将使用几种不同的技术,包括整体动物测量、SNS 活动测量和血管反应性测量。本研究的目的如下: 具体目的 1:将检验以下假设:5-HT 诱导的低血压是由 DOCA 盐和假大鼠中总外周阻力下降介导的。具体目标 2:将检验长期 5-HT 输注会降低交感神经活动或刺激感觉传入神经的假设。具体目标 3:将检验 5-HT 刺激血管受体,导致一氧化氮释放和血管松弛的假设。这项研究将填补我们对 5-HT 如何在心血管系统中发挥作用的理解空白,并探索 5-HT 在高血压中的潜在有益作用。此外,该项目可能会发现治疗原发性高血压的新治疗靶点。

项目成果

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Robert Patrick Davis其他文献

Robert Patrick Davis的其他文献

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{{ truncateString('Robert Patrick Davis', 18)}}的其他基金

Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    8437225
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
  • 项目类别:
Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    7801860
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
  • 项目类别:
Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    8209053
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
  • 项目类别:

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Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    8437225
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
  • 项目类别:
Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    7801860
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
  • 项目类别:
Mechanisms of 5-hydroxytryptamine-induced hypotension
5-羟色胺诱发低血压的机制
  • 批准号:
    8209053
  • 财政年份:
    2010
  • 资助金额:
    $ 3.91万
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