ALPHA ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW
气道血流的 ALPHA 肾上腺素调节
基本信息
- 批准号:6183929
- 负责人:
- 金额:$ 21.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-04-01 至 2002-03-31
- 项目状态:已结题
- 来源:
- 关键词:active immunization allergens alpha adrenergic agent alpha adrenergic receptor asthma bronchomotion calcium flux clinical research cyclic AMP diagnostic respiratory lavage glucocorticoids human subject inflammation laboratory rabbit norepinephrine protein kinase C receptor expression respiratory circulation respiratory hypersensitivity tissue /cell culture vascular endothelium vascular smooth muscle vasomotion
项目摘要
DESCRIPTION (Adapted from the applicant's abstract): Asthma is considered
to be an inflammatory airway disease. The airway circulation is therefore
likely to participate in some of its manifestations including exercise
induced bronchoconstriction, airway wall edema and the clearance of locally
released spasmogens. However, in contrast to airway smooth muscle
responsiveness, information on the effect of inflammation on airway vascular
smooth muscle responsiveness is lacking. The airway vasculature is part of
the systemic circulation and norepinephrine (NE) is the principal
neurotransmitter for the local adrenergic regulation of airway blood flow.
In recent studies, the principal investigator has shown that asymptomatic
asthmatics have an exaggerated vasoconstrictor response in the airway to an
inhaled adrenergic agonist and that repeated antigen challenge potentiates
NE-induced contraction of small bronchial arterial rings in sensitized
rabbits. These observations indicated that inflammation causes
alpha-adrenergic hyperresponsiveness of the airway vasculature, possibly as
an adaptive mechanism to counteract inflammatory vasodilation. The present
proposal is based on the hypothesis that the inflammatory increase in
alpha-adrenergic vascular responsiveness is due to upregulated
alpha-adrenergic signaling in vascular smooth muscle or decreased
alpha-adrenergic generation of endothelial relaxing factors, or both. This
will be tested by 1) assessing the effects of short-term and long-term
inflammatory stimulation on alpha1 and alpha2-receptor expression and
adrenergic signal transduction in rabbit bronchial arterial smooth muscle
and in endothelium, 2) correlating these findings with NE-induced bronchial
arterial contraction and its endothelial modulation, 3) comparing
alpha-adrenergic responsiveness of airway blood flow between asthmatics and
normals, and 4) determining the effect of glucocorticosteroids on enhanced
alpha-adrenergic responsiveness. These experiments are expected to yield
new information on the regulation of the airway circulation in bronchial
asthma and possibly identify novel therapeutic approaches.
描述(改编自申请者的摘要):哮喘被考虑
是一种炎症性呼吸道疾病。因此,呼吸道循环
可能参与其中的一些表现,包括锻炼
诱发的支气管收缩、气道壁水肿和局部的清除
释放出痉挛物质。然而,与呼吸道平滑肌相反,
反应性,关于炎症对呼吸道血管影响的信息
平滑肌反应性缺乏。呼吸道血管系统是
体循环和去甲肾上腺素(NE)是主要的
局部肾上腺素能调节呼吸道血流的神经递质。
在最近的研究中,首席研究人员表明,没有症状的
哮喘患者呼吸道血管收缩反应被夸大
吸入肾上腺素能激动剂和反复抗原挑战会增强
NE对致敏小鼠支气管动脉环的收缩作用
兔子。这些观察表明,炎症导致
呼吸道血管系统的α-肾上腺素能高反应性,可能是
一种抗炎性血管扩张的适应性机制。现在
这一提议是基于这样一种假设,即
α-肾上腺素能血管反应性是由于上调
α-肾上腺素能信号在血管平滑肌或减弱
α-肾上腺素能产生内皮松弛因子,或两者兼而有之。这
将通过1)评估短期和长期影响进行测试
炎症刺激对α1和α2受体表达的影响
兔支气管动脉平滑肌的肾上腺素能信号转导
在内皮方面,2)这些发现与去甲肾上腺素诱导的支气管
动脉收缩及其内皮调节,3)比较
哮喘患者和哮喘患者呼吸道血流的α-肾上腺素能反应性
正常,以及4)测定糖皮质激素对增强的影响
α-肾上腺素能反应。这些实验预计将产生
支气管呼吸道循环调节的新进展
哮喘,并可能找到新的治疗方法。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Systemic ovalbumin sensitization downregulates norepinephrine uptake by rabbit aortic smooth muscle cells.
全身卵清蛋白致敏下调兔主动脉平滑肌细胞去甲肾上腺素的摄取。
- DOI:10.1165/rcmb.2002-0030oc
- 发表时间:2002
- 期刊:
- 影响因子:6.4
- 作者:Horvath,Gabor;Torbati,Aliza;Conner,GregoryE;Salathe,Matthias;Wanner,Adam
- 通讯作者:Wanner,Adam
Altered contractile sensitivity of isolated bronchial artery to phenylephrine in ovalbumin-sensitized rabbits.
改变卵清蛋白致敏兔离体支气管动脉对去氧肾上腺素的收缩敏感性。
- DOI:10.1152/jappl.1999.86.5.1721
- 发表时间:1999
- 期刊:
- 影响因子:0
- 作者:Zschauer,AO;Sielczak,MW;Wanner,A
- 通讯作者:Wanner,A
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Adam Wanner其他文献
Adam Wanner的其他文献
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{{ truncateString('Adam Wanner', 18)}}的其他基金
ALPHA ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW
气道血流的 ALPHA 肾上腺素调节
- 批准号:
2865284 - 财政年份:1998
- 资助金额:
$ 21.87万 - 项目类别:
ALPHA ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW
气道血流的 ALPHA 肾上腺素调节
- 批准号:
2901299 - 财政年份:1998
- 资助金额:
$ 21.87万 - 项目类别:
ALPHA-ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW
气道血流的α-肾上腺素调节
- 批准号:
2471560 - 财政年份:1998
- 资助金额:
$ 21.87万 - 项目类别:
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