ALPHA ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW

气道血流的 ALPHA 肾上腺素调节

• 批准号: 2865284
• 负责人: Adam Wanner
• 金额: $ 17.28万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2865284
• 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

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（改编自申请人摘要）：考虑哮喘